Editing Gibberellin

{{Short description|Class of plant hormones}}
{{Overly detailed|date=September 2019}}
'''Gibberellins''' ('''GAs''') are [[plant hormone]]s that regulate various [[Biological process|developmental processes]], including [[Plant stem|stem]] elongation, [[germination]], [[dormancy]], [[flowering]], [[flower]] development, and leaf and fruit [[senescence]].<ref name="Hedden-2015" /> They are one of the longest-known classes of plant hormone. It is thought that the [[selective breeding]] (albeit unconscious) of crop strains that were deficient in GA synthesis was one of the key drivers of the "[[Green Revolution|green revolution]]" in the 1960s,<ref name="Spielmeyer-2002">{{cite journal|vauthors=Spielmeyer W, Ellis MH, Chandler PM|date=June 2002|title=Semidwarf (sd-1), "green revolution" rice, contains a defective gibberellin 20-oxidase gene|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=99|issue=13|pages=9043–8|doi=10.1073/pnas.132266399|pmc=124420|pmid=12077303|bibcode=2002PNAS...99.9043S|doi-access=free}}</ref> a revolution that is credited to have saved over a billion lives worldwide.<ref>{{Cite web|url=http://www.agbioworld.org/biotech-info/topics/borlaug/special.html|title=Norman Borlaug: A Billion Lives Saved|website=www.agbioworld.org|access-date=2018-05-11}}</ref>

==Chemistry==
All known gibberellins are [[Diterpene#Diterpenoids|diterpenoid]] acids synthesized by the terpenoid pathway in [[plastid]]s and then modified in the [[endoplasmic reticulum]] and [[cytosol]] until they reach their biologically active form.<ref name="Campbell-2002">{{cite book | vauthors = Campbell N, Reec JB | author-link1 = Neil Campbell (scientist) | title = Biology | url = https://archive.org/details/biologyc00camp | url-access = registration | edition = 6th | location = San Francisco | publisher = Benjamin Cummings | year = 2002 | isbn = 9780805366242 }}</ref> All are derived via the ''ent''-gibberellane skeleton but are synthesised via ''ent''-kaurene. The gibberellins are named GA<sub>1</sub> through GA<sub>n</sub> in order of discovery.<ref name="Sponsel-2010">{{Citation|last1=Sponsel|first1=Valerie M.|title=Gibberellin Biosynthesis and Inactivation|date=2010|url=http://link.springer.com/10.1007/978-1-4020-2686-7_4|work=Plant Hormones|pages=63–94|editor-last=Davies|editor-first=Peter J.|place=Dordrecht|publisher=Springer Netherlands|language=en|doi=10.1007/978-1-4020-2686-7_4|isbn=978-1-4020-2684-3|access-date=2022-01-29|last2=Hedden|first2=Peter|url-access=subscription}}</ref> [[Gibberellic acid]], which was the first gibberellin to be structurally characterized, is GA<sub>3</sub>.<ref name="Hedden-2020">{{Cite journal|last=Hedden|first=Peter|date=2020-11-23|title=The Current Status of Research on Gibberellin Biosynthesis|url=https://doi.org/10.1093/pcp/pcaa092|journal=Plant and Cell Physiology|volume=61|issue=11|pages=1832–1849|doi=10.1093/pcp/pcaa092|issn=1471-9053|pmc=7758035|pmid=32652020}}</ref>

{{As of|2020}},<ref name="Sponsel-2010" /> there are 136 GAs identified from plants, fungi, and bacteria.<ref name="Hedden-2015" /><ref name="Hedden-2020" /><ref name="Sponsel-2010" />

Gibberellins are tetracyclic diterpene acids. There are two classes, with either 19 or 20 carbons. The 19-carbon gibberellins are generally the biologically active forms. They have lost carbon 20 and, in place, possess a five-member [[lactone]] bridge that links carbons 4 and 10. [[Hydroxylation]] also has a great effect on its biological activity. In general, the most biologically active compounds are dihydroxylated gibberellins, with hydroxyl groups on both carbons 3 and 13. Gibberellic acid is a 19-carbon dihydroxylated gibberellin.<ref name="AccessScience">{{cite journal | doi = 10.1036/1097-8542.289000 | title=Gibberellins | journal=AccessScience}}</ref>

===Bioactive GAs===
The bioactive Gibberellins are GA<sub>1</sub>, GA<sub>3</sub>, GA<sub>4</sub>, and GA<sub>7</sub>.<ref name="Yamaguchi-2008">{{cite journal | vauthors = Yamaguchi S | title = Gibberellin metabolism and its regulation | journal = Annual Review of Plant Biology | volume = 59 | pages = 225–51 | year = 2008 | pmid = 18173378 | doi = 10.1146/annurev.arplant.59.032607.092804 }}</ref> There are three common structural traits between these GAs: 1) hydroxyl group on C-3β, 2) a carboxyl group on carbon 6, and 3) a lactone between carbons 4 and 10.<ref name="Yamaguchi-2008" /> 

<gallery perrow="4">
File:Gibberellin A1 v2.svg|{{center|Gibberellin A<sub>1</sub> (GA<sub>1</sub>)}}
File:Gibberellic acid.svg|{{center|[[Gibberellic acid]] (GA<sub>3</sub>)}}
File:Ent-Gibberellane.svg|{{center|''ent''-Gibberellane}}
File:Ent-Kauren.svg|{{center|''ent''-Kaurene}}
</gallery>

The 3β-hydroxyl group can be exchanged for other functional groups at C-2 and/or C-3 positions.<ref name="Yamaguchi-2008" /> GA<sub>5</sub> and GA<sub>6</sub> are examples of bioactive GAs without a hydroxyl group on C-3β.<ref name="Yamaguchi-2008" /> The presence of GA<sub>1</sub> in various plant species suggests that it is a common bioactive GA.<ref>{{cite journal | vauthors = MacMillan J | title = Occurrence of Gibberellins in Vascular Plants, Fungi, and Bacteria | journal = Journal of Plant Growth Regulation | volume = 20 | issue = 4 | pages = 387–442 | date = December 2001 | pmid = 11986764 | doi = 10.1007/s003440010038 | s2cid = 44504525 }}</ref>

==Biological function==
[[File:The effect of Gibberellins.svg|thumb|1. Shows a plant lacking gibberellins, and which and has an [[Plant stem|internode]] length of "0" as well as being a dwarf plant. 2. Shows an average plant with a moderate amount of gibberellins, and an average internode length. 3. Shows a plant with a large amount of gibberellins and so has a much longer internode length, because gibberellins promote cell division in the stem.]]Gibberellins are involved in the natural process of breaking [[dormancy]] and other aspects of [[germination]]. Before the photosynthetic apparatus develops sufficiently in the early stages of germination, the seed reserves of [[starch]] nourish the seedling. Usually in germination, the breakdown of starch to [[glucose]] in the [[endosperm]] begins shortly after the seed is exposed to water.<ref>{{cite journal | last1 = Davies | first1 = Peter J. | name-list-style = vanc | title = Plant growth | journal = AccessScience | doi = 10.1036/1097-8542.523000 }}</ref> Gibberellins in the seed embryo are believed to signal starch [[hydrolysis]] through inducing the synthesis of the enzyme α-[[amylase]] in the aleurone cells. In the model for gibberellin-induced production of α-amylase, it is demonstrated that gibberellins from the [[scutellum (botany)|scutellum]] diffuse to the aleurone cells, where they stimulate the secretion α-amylase.<ref name="Campbell-2002" /> α-Amylase then hydrolyses starch (abundant in many seeds), into glucose that can be used to produce energy for the seed embryo. Studies of this process have indicated gibberellins cause higher levels of [[transcription (genetics)|transcription]] of the gene coding for the α-amylase enzyme, to stimulate the synthesis of α-amylase.<ref name="AccessScience" />

Exposition to cold temperatures increases the production of Gibberellins. They stimulate cell elongation, breaking and budding, and seedless fruits. Gibberellins cause also seed germination by breaking the seed's dormancy and acting as a chemical messenger. Its hormone binds to a receptor, and [[calcium]] activates the protein [[calmodulin]], and the complex binds to DNA, producing an enzyme to stimulate growth in the embryo.

==Metabolism==
===Biosynthesis===
Gibberellins are usually synthesized from the [[methylerythritol phosphate]] (MEP) pathway in higher plants.<ref name="Hedden-2012">{{cite journal | vauthors = Hedden P, Thomas SG | s2cid = 25627726 | title = Gibberellin biosynthesis and its regulation | journal = The Biochemical Journal | volume = 444 | issue = 1 | pages = 11–25 | date = May 2012 | pmid = 22533671 | doi = 10.1042/BJ20120245 }}</ref> In this pathway, bioactive GA is produced from [[trans-geranylgeranyl diphosphate|''trans''-geranylgeranyl diphosphate]] (GGDP), with the participation of three classes of enzymes: terpene syntheses (TPSs), [[Cytochrome P450 monooxygenase system|cytochrome P450 monooxygenases]] (P450s), and [[2-oxoglutarate–dependent dioxygenase]]s (2ODDs).<ref name="Hedden-2012" /><ref name="Yamaguchi-2008" /> The MEP pathway follows eight steps:<ref name="Yamaguchi-2008" />

# GGDP is converted to ent-copalyl diphosphate (ent-CDP) by [[ent-copalyl diphosphate synthase|''ent''-copalyl diphosphate synthase]] (CPS)
# ent-CDP is converted to ent-kaurene by [[ent-kaurene synthase|''ent''-kaurene synthase]] (KS)
# ent-kaurene is converted to ent-kaurenol by [[ent-kaurene oxidase|''ent''-kaurene oxidase]] (KO)
# ent-kaurenol is converted to ent-kaurenal by KO
# ent-kaurenal is converted to ent-kaurenoic acid by KO
# [[ent-kaurenoic acid]] is converted to ent-7a-hydroxykaurenoic acid by [[ent-kaurenoic acid oxidase|''ent''-kaurenoic acid oxidase]] (KAO)
# ent-7a-hydroxykaurenoic acid is converted to GA12-aldehyde by KAO
# GA12-aldehyde is converted to GA12 by KAO. GA12 is processed to the bioactive GA4 by oxidations on C-20 and C-3, which is accomplished by 2 soluble ODDs: GA 20-oxidase and GA 3-oxidase.

One or two genes encode the enzymes responsible for the first steps of GA biosynthesis in ''[[Arabidopsis]]'' and rice.<ref name="Yamaguchi-2008" /> The null alleles of the genes encoding CPS, KS, and KO result in GA-deficient ''Arabidopsis'' dwarves.<ref>{{cite journal | vauthors = Koornneef M, van der Veen JH | title = Induction and analysis of gibberellin sensitive mutants in Arabidopsis thaliana (L.) heynh | journal = Theoretical and Applied Genetics | volume = 58 | issue = 6 | pages = 257–63 | date = November 1980 | pmid = 24301503 | doi = 10.1007/BF00265176 | s2cid = 22824299 }}</ref> Multigene families encode the 2ODDs that catalyze the formation of GA<sub>12</sub> to bioactive GA<sub>4</sub>.<ref name="Yamaguchi-2008" />

AtGA3ox1 and AtGA3ox2, two of the four genes that encode GA3ox in ''Arabidopsis'', affect vegetative development.<ref>{{cite journal | vauthors = Mitchum MG, Yamaguchi S, Hanada A, Kuwahara A, Yoshioka Y, Kato T, Tabata S, Kamiya Y, Sun TP | title = Distinct and overlapping roles of two gibberellin 3-oxidases in Arabidopsis development | journal = The Plant Journal | volume = 45 | issue = 5 | pages = 804–18 | date = March 2006 | pmid = 16460513 | doi = 10.1111/j.1365-313X.2005.02642.x | doi-access = free }}</ref> Environmental stimuli regulate AtGA3ox1 and AtGA3ox2 activity during seed germination.<ref name="Yamaguchi-1998">{{cite journal | vauthors = Yamaguchi S, Smith MW, Brown RG, Kamiya Y, Sun T | title = Phytochrome regulation and differential expression of gibberellin 3beta-hydroxylase genes in germinating Arabidopsis seeds | journal = The Plant Cell | volume = 10 | issue = 12 | pages = 2115–26 | date = December 1998 | pmid = 9836749 | pmc = 143973 | doi = 10.1105/tpc.10.12.2115 }}</ref><ref name="Yamauchi-2004">{{cite journal | vauthors = Yamauchi Y, Ogawa M, Kuwahara A, Hanada A, Kamiya Y, Yamaguchi S | title = Activation of gibberellin biosynthesis and response pathways by low temperature during imbibition of Arabidopsis thaliana seeds | journal = The Plant Cell | volume = 16 | issue = 2 | pages = 367–78 | date = February 2004 | pmid = 14729916 | pmc = 341910 | doi = 10.1105/tpc.018143 }}</ref> In ''Arabidopsis'', GA20ox overexpression leads to an increase in GA concentration.<ref>{{cite journal | vauthors = Coles JP, Phillips AL, Croker SJ, García-Lepe R, Lewis MJ, Hedden P | title = Modification of gibberellin production and plant development in Arabidopsis by sense and antisense expression of gibberellin 20-oxidase genes | journal = The Plant Journal | volume = 17 | issue = 5 | pages = 547–56 | date = March 1999 | pmid = 10205907 | doi = 10.1046/j.1365-313X.1999.00410.x }}</ref><ref>{{cite journal | vauthors = Huang S, Raman AS, Ream JE, Fujiwara H, Cerny RE, Brown SM | title = Overexpression of 20-oxidase confers a gibberellin-overproduction phenotype in Arabidopsis | journal = Plant Physiology | volume = 118 | issue = 3 | pages = 773–81 | date = November 1998 | pmid = 9808721 | pmc = 34787 | doi = 10.1104/pp.118.3.773 }}</ref>

====Sites of biosynthesis====
Most bioactive Gibberellins are located in actively growing organs on plants.<ref name="Hedden-2012" /> Both GA20ox and GA3ox genes (genes coding for GA 20-oxidase and GA 3-oxidase) and the SLENDER1 gene (a GA [[signal transduction]] gene) are found in growing organs on rice, which suggests bioactive GA synthesis occurs at their site of action in growing organs in plants.<ref name="Kaneko-2003">{{cite journal | vauthors = Kaneko M, Itoh H, Inukai Y, Sakamoto T, Ueguchi-Tanaka M, Ashikari M, Matsuoka M | title = Where do gibberellin biosynthesis and gibberellin signaling occur in rice plants? | journal = The Plant Journal | volume = 35 | issue = 1 | pages = 104–15 | date = July 2003 | pmid = 12834406 | doi = 10.1046/j.1365-313X.2003.01780.x | doi-access = free }}</ref> During flower development, the tapetum of anthers is believed to be a primary site of GA biosynthesis.<ref name="Kaneko-2003" /><ref>{{cite journal | vauthors = Itoh H, Tanaka-Ueguchi M, Kawaide H, Chen X, Kamiya Y, Matsuoka M | title = The gene encoding tobacco gibberellin 3beta-hydroxylase is expressed at the site of GA action during stem elongation and flower organ development | journal = The Plant Journal | volume = 20 | issue = 1 | pages = 15–24 | date = October 1999 | pmid = 10571861 | doi = 10.1046/j.1365-313X.1999.00568.x | doi-access = free }}</ref>

====Differences between biosynthesis in fungi and lower plants====
The flower ''Arabidopsis'' and the fungus ''[[Gibberella fujikuroi]]'' possess different GA pathways and enzymes.<ref name="Yamaguchi-2008" /> P450s in fungi perform functions analogous to the functions of KAOs in plants.<ref>{{cite journal | vauthors = Rojas MC, Hedden P, Gaskin P, Tudzynski B | title = The P450-1 gene of Gibberella fujikuroi encodes a multifunctional enzyme in gibberellin biosynthesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 10 | pages = 5838–43 | date = May 2001 | pmid = 11320210 | pmc = 33300 | doi = 10.1073/pnas.091096298 | bibcode = 2001PNAS...98.5838R | doi-access = free }}</ref> The function of CPS and KS in plants is performed by a single enzyme in fungi (CPS/KS).<ref>{{cite journal | vauthors = Kawaide H, Imai R, Sassa T, Kamiya Y | title = Ent-kaurene synthase from the fungus Phaeosphaeria sp. L487. cDNA isolation, characterization, and bacterial expression of a bifunctional diterpene cyclase in fungal gibberellin biosynthesis | journal = The Journal of Biological Chemistry | volume = 272 | issue = 35 | pages = 21706–12 | date = August 1997 | pmid = 9268298 | doi = 10.1074/jbc.272.35.21706 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Toyomasu T, Kawaide H, Ishizaki A, Shinoda S, Otsuka M, Mitsuhashi W, Sassa T | title = Cloning of a full-length cDNA encoding ent-kaurene synthase from Gibberella fujikuroi: functional analysis of a bifunctional diterpene cyclase | journal = Bioscience, Biotechnology, and Biochemistry | volume = 64 | issue = 3 | pages = 660–4 | date = March 2000 | pmid = 10803977 | doi = 10.1271/bbb.64.660 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tudzynski B, Kawaide H, Kamiya Y | title = Gibberellin biosynthesis in Gibberella fujikuroi: cloning and characterization of the copalyl diphosphate synthase gene | journal = Current Genetics | volume = 34 | issue = 3 | pages = 234–40 | date = September 1998 | pmid = 9745028 | doi = 10.1007/s002940050392 | s2cid = 3021994 }}</ref> In plants the Gibberellin biosynthesis genes are found randomly on multiple chromosomes, but in fungi are found on one chromosome
.<ref>{{cite journal | vauthors = Hedden P, Phillips AL, Rojas MC, Carrera E, Tudzynski B | title = Gibberellin Biosynthesis in Plants and Fungi: A Case of Convergent Evolution? | journal = Journal of Plant Growth Regulation | volume = 20 | issue = 4 | pages = 319–331 | date = December 2001 | pmid = 11986758 | doi = 10.1007/s003440010037 | s2cid = 25623658 }}</ref><ref>{{cite journal | vauthors = Kawaide H | title = Biochemical and molecular analyses of gibberellin biosynthesis in fungi | journal = Bioscience, Biotechnology, and Biochemistry | volume = 70 | issue = 3 | pages = 583–90 | date = March 2006 | pmid = 16556972 | doi = 10.1271/bbb.70.583 | s2cid = 20952424 | doi-access = free }}</ref> 

Plants produce low amount of Gibberellic Acid, therefore is produced for industrial purposes by microorganisms. Industrially GA<sub>3</sub> can be produced by submerged fermentation, but this process presents low yield with high production costs and hence higher sale value, nevertheless other alternative process to reduce costs of its production is [[solid-state fermentation]] (SSF) that allows the use of agro-industrial residues.<ref>{{cite journal | vauthors = Lopes AL, Silva DN, Rodrigues C, Costa JL, Machado MP, Penha RO, Biasi LA, Ricardo C | title = Gibberellic acid fermented extract obtained by solid-state fermentation using citric pulp by Fusarium moniliforme: Influence on Lavandula angustifolia Mill. cultivated in vitro | journal = Pak J Bot. | year = 2013 | volume = 45 | pages = 2057–2064 }}</ref>

===Catabolism===
Several mechanisms for inactivating Giberellins have been identified. 2β-hydroxylation deactivates them, and is catalyzed by GA2-oxidases (GA2oxs).<ref name="Hedden-2012" /> Some GA2oxs use 19-carbon Gibberellins as substrates, while other use C20-GAs.<ref name="Thomas-1999">{{cite journal | vauthors = Thomas SG, Phillips AL, Hedden P | title = Molecular cloning and functional expression of gibberellin 2- oxidases, multifunctional enzymes involved in gibberellin deactivation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 8 | pages = 4698–703 | date = April 1999 | pmid = 10200325 | doi = 10.1073/pnas.96.8.4698 | pmc = 16395 | bibcode = 1999PNAS...96.4698T | doi-access = free }}</ref><ref>{{cite journal | vauthors = Schomburg FM, Bizzell CM, Lee DJ, Zeevaart JA, Amasino RM | title = Overexpression of a novel class of gibberellin 2-oxidases decreases gibberellin levels and creates dwarf plants | journal = The Plant Cell | volume = 15 | issue = 1 | pages = 151–63 | date = January 2003 | pmid = 12509528 | pmc = 143488 | doi = 10.1105/tpc.005975 }}</ref> Cytochrome P450 mono-oxygenase, encoded by elongated uppermost internode (eui), converts Gibberellins into 16α,17-epoxides.<ref name="Zhu-2006">{{cite journal | vauthors = Zhu Y, Nomura T, Xu Y, Zhang Y, Peng Y, Mao B, Hanada A, Zhou H, Wang R, Li P, Zhu X, Mander LN, Kamiya Y, Yamaguchi S, He Z | title = ELONGATED UPPERMOST INTERNODE encodes a cytochrome P450 monooxygenase that epoxidizes gibberellins in a novel deactivation reaction in rice | journal = The Plant Cell | volume = 18 | issue = 2 | pages = 442–56 | date = February 2006 | pmid = 16399803 | pmc = 1356550 | doi = 10.1105/tpc.105.038455 }}</ref> Rice eui mutants amass bioactive Gibberellins at high levels, which suggests cytochrome P450 mono-oxygenase is a main enzyme responsible for deactivation GA in rice.<ref name="Zhu-2006" /> The Gamt1 and gamt2 genes encode enzymes that methylate the C-6 carboxyl group of GAs.<ref name="Varbanova-2007">{{cite journal | vauthors = Varbanova M, Yamaguchi S, Yang Y, McKelvey K, Hanada A, Borochov R, Yu F, Jikumaru Y, Ross J, Cortes D, Ma CJ, Noel JP, Mander L, Shulaev V, Kamiya Y, Rodermel S, Weiss D, Pichersky E | title = Methylation of gibberellins by Arabidopsis GAMT1 and GAMT2 | journal = The Plant Cell | volume = 19 | issue = 1 | pages = 32–45 | date = January 2007 | pmid = 17220201 | pmc = 1820973 | doi = 10.1105/tpc.106.044602 }}</ref> In a gamt1 and gamt2 mutant, concentrations of GA in developing seeds is increased.<ref name="Varbanova-2007" />

===Homeostasis===
Feedback and feedforward regulation maintains the levels of bioactive Gibberellins in plants.<ref>{{cite journal | vauthors = Hedden P, Phillips AL | title = Gibberellin metabolism: new insights revealed by the genes | journal = Trends in Plant Science | volume = 5 | issue = 12 | pages = 523–30 | date = December 2000 | pmid = 11120474 | doi = 10.1016/S1360-1385(00)01790-8 }}</ref><ref>{{cite journal | vauthors = Olszewski N, Sun TP, Gubler F | title = Gibberellin signaling: biosynthesis, catabolism, and response pathways | journal = The Plant Cell | volume = 14 Suppl | issue = Suppl | pages = S61–80 | year = 2002 | pmid = 12045270 | pmc = 151248 | doi = 10.1105/tpc.010476 }}</ref> Levels of AtGA20ox1 and AtGA3ox1 expression are increased in a Gibberellin deficient environment, and decreased after the addition of bioactive GAs,<ref name="Yamaguchi-1998" /><ref>{{cite journal | vauthors = Chiang HH, Hwang I, Goodman HM | title = Isolation of the Arabidopsis GA4 locus | journal = The Plant Cell | volume = 7 | issue = 2 | pages = 195–201 | date = February 1995 | pmid = 7756830 | pmc = 160775 | doi = 10.1105/tpc.7.2.195 }}</ref><ref>{{cite journal | vauthors = Matsushita A, Furumoto T, Ishida S, Takahashi Y | title = AGF1, an AT-hook protein, is necessary for the negative feedback of AtGA3ox1 encoding GA 3-oxidase | journal = Plant Physiology | volume = 143 | issue = 3 | pages = 1152–62 | date = March 2007 | pmid = 17277098 | pmc = 1820926 | doi = 10.1104/pp.106.093542 }}</ref><ref>{{cite journal | vauthors = Phillips AL, Ward DA, Uknes S, Appleford NE, Lange T, Huttly AK, Gaskin P, Graebe JE, Hedden P | title = Isolation and expression of three gibberellin 20-oxidase cDNA clones from Arabidopsis | journal = Plant Physiology | volume = 108 | issue = 3 | pages = 1049–57 | date = July 1995 | pmid = 7630935 | pmc = 157456 | doi = 10.1104/pp.108.3.1049 }}</ref><ref>{{cite journal | vauthors = Xu YL, Li L, Gage DA, Zeevaart JA | title = Feedback regulation of GA5 expression and metabolic engineering of gibberellin levels in Arabidopsis | journal = The Plant Cell | volume = 11 | issue = 5 | pages = 927–36 | date = May 1999 | pmid = 10330476 | pmc = 144230 | doi = 10.1105/tpc.11.5.927 }}</ref> Conversely, expression of the Gibberellin deactivation genes AtGA2ox1 and AtGA2ox2 is increased with addition of Gibberellins.<ref name="Thomas-1999" />

==Regulation==

===Regulation by other hormones===
The auxin indole-3-acetic acid (IAA) regulates concentration of GA<sub>1</sub> in elongating internodes in peas.<ref name="Ross-2000">{{cite journal | vauthors = Ross JJ, O'Neill DP, Smith JJ, Kerckhoffs LH, Elliott RC | title = Evidence that auxin promotes gibberellin A1 biosynthesis in pea | journal = The Plant Journal | volume = 21 | issue = 6 | pages = 547–52 | date = March 2000 | pmid = 10758505 | doi = 10.1046/j.1365-313x.2000.00702.x | doi-access = free }}</ref> Removal of IAA by removal of the apical bud, the auxin source, reduces the concentration of GA<sub>1</sub>, and reintroduction of IAA reverses these effects to increase the concentration of GA<sub>1</sub>.<ref name="Ross-2000" /> This has also been observed in tobacco plants.<ref>{{cite journal | vauthors = Wolbang CM, Ross JJ | title = Auxin promotes gibberellin biosynthesis in decapitated tobacco plants | journal = Planta | volume = 214 | issue = 1 | pages = 153–7 | date = November 2001 | pmid = 11762165 | doi = 10.1007/s004250100663 | bibcode = 2001Plant.214..153W | s2cid = 31185063 | url = http://ecite.utas.edu.au/22964 }}</ref> Auxin increases GA 3-oxidation and decreases GA 2-oxidation in barley.<ref>{{cite journal | vauthors = Wolbang CM, Chandler PM, Smith JJ, Ross JJ | title = Auxin from the developing inflorescence is required for the biosynthesis of active gibberellins in barley stems | journal = Plant Physiology | volume = 134 | issue = 2 | pages = 769–76 | date = February 2004 | pmid = 14730077 | pmc = 344552 | doi = 10.1104/pp.103.030460 }}</ref> Auxin also regulates GA biosynthesis during fruit development in peas.<ref>{{cite journal | vauthors = Ngo P, Ozga JA, Reinecke DM | title = Specificity of auxin regulation of gibberellin 20-oxidase gene expression in pea pericarp | journal = Plant Molecular Biology | volume = 49 | issue = 5 | pages = 439–48 | date = July 2002 | pmid = 12090620 | doi = 10.1023/A:1015522404586 | s2cid = 22530544 }}</ref> These discoveries in different plant species suggest the auxin regulation of GA metabolism may be a universal mechanism.

Ethylene decreases the concentration of bioactive GAs.<ref>{{cite journal | vauthors = Achard P, Baghour M, Chapple A, Hedden P, Van Der Straeten D, Genschik P, Moritz T, Harberd NP | title = The plant stress hormone ethylene controls floral transition via DELLA-dependent regulation of floral meristem-identity genes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 15 | pages = 6484–9 | date = April 2007 | pmid = 17389366 | pmc = 1851083 | doi = 10.1073/pnas.0610717104 | bibcode = 2007PNAS..104.6484A | doi-access = free }}</ref>

===Regulation by environmental factors===
Recent evidence suggests fluctuations in GA concentration influence light-regulated seed germination, [[photomorphogenesis]] during [[de-etiolation]], and [[Photoperiodism|photoperiod]] regulation of stem elongation and flowering.<ref name="Yamaguchi-2008" /> Microarray analysis showed about one fourth cold-responsive genes are related to GA-regulated genes, which suggests GA influences response to cold temperatures.<ref name="Yamauchi-2004" /> Plants reduce growth rate when exposed to stress. A relationship between GA levels and amount of stress experienced has been suggested in barley.<ref>{{cite journal | vauthors = Vettakkorumakankav NN, Falk D, Saxena P, Fletcher RA |title=A Crucial Role for Gibberellins in Stress Protection of Plants|journal=Plant and Cell Physiology|year=1999|volume=40|pages=542–548|doi=10.1093/oxfordjournals.pcp.a029575|issue=5|doi-access=free}}</ref>

===Role in seed development===
Bioactive GAs and [[abscisic acid]] (ABA) levels have an inverse relationship and regulate seed development and germination.<ref>{{cite journal | vauthors = Batge SL, Ross JJ, Reid JB |title=Abscisic acid levels in seeds of the gibberellin-deficient mutant lh-2 of pea (Pisum sativum)|journal=Physiologia Plantarum|year=1999|volume=195|pages=485–490|doi=10.1034/j.1399-3054.1999.105313.x|issue=3|doi-access=free}}</ref><ref>{{cite journal | vauthors = White CN, Proebsting WM, Hedden P, Rivin CJ | title = Gibberellins and seed development in maize. I. Evidence that gibberellin/abscisic acid balance governs germination versus maturation pathways | journal = Plant Physiology | volume = 122 | issue = 4 | pages = 1081–8 | date = April 2000 | pmid = 10759503 | pmc = 58942 | doi = 10.1104/pp.122.4.1081 }}</ref> Levels of FUS3, an ''Arabidopsis'' transcription factor, are upregulated by ABA and downregulated by Giberellins, which suggests that there is a regulation loop that establishes the balance of Gibberellins and Abscisic Acid.<ref>{{cite journal | vauthors = Gazzarrini S, Tsuchiya Y, Lumba S, Okamoto M, McCourt P | title = The transcription factor FUSCA3 controls developmental timing in Arabidopsis through the hormones gibberellin and abscisic acid | journal = Developmental Cell | volume = 7 | issue = 3 | pages = 373–85 | date = September 2004 | pmid = 15363412 | doi = 10.1016/j.devcel.2004.06.017 | doi-access = free }}</ref>

In the practice, this means that farmers can alter this balance to make all fruits mature a little later, at a same time, or 'glue' the fruit in the trees until the harvest day (because ABA participates in the maturation of the fruits, and many crops mature and drop a few fruits a day for several weeks, that is undesirable for markets).

==Signalling mechanism==

=== Receptor ===
In the early 1990s, there were several lines of evidence that suggested the existence of a GA receptor in [[oat]] seeds located at the [[Cell membrane|plasma membrane]]. However, despite intensive research, to date, no membrane-bound GA receptor has been isolated. This, along with the discovery of a soluble receptor, GA insensitive dwarf 1 (GID1) has led many to doubt that a membrane-bound receptor exists.<ref name="Hedden-2015">{{cite journal | vauthors = Hedden P, Sponsel V | title = A Century of Gibberellin Research | journal = Journal of Plant Growth Regulation | volume = 34 | issue = 4 | pages = 740–60 | date = 2015 | pmid = 26523085 | pmc = 4622167 | doi = 10.1007/s00344-015-9546-1 }}</ref>[[File:GA signal cascade.png|thumb|280x280px|'''GA-GID1-DELLA signal pathway:''' In the absence of GA, DELLA proteins bind to and inhibit transcription factors (TFs) and prefoldins (PFDs). When GA is present, GID1 triggers the degradation of DELLAs and releases the TFs and PFDs.]]GID1 was first identified in [[rice]]<ref name="Ueguchi-Tanaka-2007">{{cite journal|vauthors=Ueguchi-Tanaka M, Nakajima M, Katoh E, Ohmiya H, Asano K, Saji S, Hongyu X, Ashikari M, Kitano H, Yamaguchi I, Matsuoka M|date=July 2007|title=Molecular interactions of a soluble gibberellin receptor, GID1, with a rice DELLA protein, SLR1, and gibberellin|journal=The Plant Cell|volume=19|issue=7|pages=2140–55|doi=10.1105/tpc.106.043729|pmc=1955699|pmid=17644730}}</ref> and in ''Arabidopsis'' there are three orthologs of GID1, AtGID1a, b, and c.<ref name="Hedden-2015" /> GID1s have a high affinity for [[Bioactive compound|bioactive]] GAs.<ref name="Ueguchi-Tanaka-2007" /> GA binds to a specific binding pocket on GID1; the C3-hydroxyl on GA makes contact with tyrosine-31 in the GID1 binding pocket.<ref name="Murase-2008">{{cite journal | vauthors = Murase K, Hirano Y, Sun TP, Hakoshima T | title = Gibberellin-induced DELLA recognition by the gibberellin receptor GID1 | journal = Nature | volume = 456 | issue = 7221 | pages = 459–63 | date = November 2008 | pmid = 19037309 | doi = 10.1038/nature07519 | bibcode = 2008Natur.456..459M | s2cid = 16280595 }}</ref><ref name="Shimada-2008">{{cite journal | vauthors = Shimada A, Ueguchi-Tanaka M, Nakatsu T, Nakajima M, Naoe Y, Ohmiya H, Kato H, Matsuoka M | title = Structural basis for gibberellin recognition by its receptor GID1 | journal = Nature | volume = 456 | issue = 7221 | pages = 520–3 | date = November 2008 | pmid = 19037316 | doi = 10.1038/nature07546 | bibcode = 2008Natur.456..520S | s2cid = 205215510 }}</ref> GA binding to GID1 causes changes in GID1 structure, causing a 'lid' on GID1 to cover the GA binding pocket. The movement of this lid results in the exposure of a surface which enables the binding of GID1 to DELLA proteins.<ref name="Murase-2008" /><ref name="Shimada-2008" />

===DELLA proteins: Repression of a repressor===
DELLA proteins (such as SLR1 in rice or [[GAI (Arabidopsis thaliana gene)|GAI]] and RGA in ''Arabidopsis'') are repressors of plant development, characterized by the presence of a DELLA motif ([[Aspartic acid|aspartate]]-[[Glutamic acid|glutamate]]-[[leucine]]-leucine-[[alanine]] or D-E-L-L-A in the single letter [[amino acid code]]).<ref name="Davière-2013" />

DELLAs inhibit seed germination, seed growth, flowering and GA reverses these effects.<ref>{{cite journal | vauthors = Achard P, Genschik P | title = Releasing the brakes of plant growth: how GAs shutdown DELLA proteins | journal = Journal of Experimental Botany | volume = 60 | issue = 4 | pages = 1085–92 | year = 2009 | pmid = 19043067 | doi = 10.1093/jxb/ern301 | doi-access = free }}</ref> 
When Gibberellins bind to the GID1 receptor, it enhances the interaction between GID1 and DELLA proteins, forming a GA-GID1-DELLA complex. In that complex it is thought that the structure of DELLA proteins experience changes, enabling  their binding to [[F-box protein]]s for their degradation.<ref name="Lechner-2006">{{cite journal | vauthors = Lechner E, Achard P, Vansiri A, Potuschak T, Genschik P | title = F-box proteins everywhere | journal = Current Opinion in Plant Biology | volume = 9 | issue = 6 | pages = 631–8 | date = December 2006 | pmid = 17005440 | doi = 10.1016/j.pbi.2006.09.003 | bibcode = 2006COPB....9..631L }}</ref><ref name="Davière-2013">{{cite journal | vauthors = Davière JM, Achard P | title = Gibberellin signaling in plants | journal = Development | volume = 140 | issue = 6 | pages = 1147–51 | date = March 2013 | pmid = 23444347 | doi = 10.1242/dev.087650 | doi-access = free }}</ref><ref>{{cite journal | vauthors = McGinnis KM, Thomas SG, Soule JD, Strader LC, Zale JM, Sun TP, Steber CM | title = The Arabidopsis SLEEPY1 gene encodes a putative F-box subunit of an SCF E3 ubiquitin ligase | journal = The Plant Cell | volume = 15 | issue = 5 | pages = 1120–30 | date = May 2003 | pmid = 12724538 | pmc = 153720 | doi = 10.1105/tpc.010827 }}</ref> F-box proteins (SLY1 in ''Arabidopsis'' or GID2 in rice) [[Catalysis|catalyse]] the addition of [[ubiquitin]] to their targets.<ref name="Lechner-2006" /> Adding ubiquitin to DELLA proteins promotes their degradation via the [[Proteasome|26S-proteosome]].<ref name="Davière-2013" /> This releases cells from DELLAs repressive effects.

=== Targets of DELLA proteins ===

==== Transcription factors ====
The first targets of DELLA proteins identified were Phytochrome Interacting Factors (PIFs). PIFs are [[transcription factor]]s that negatively regulate light signalling and are strong promoters of elongation growth. In the presence of GA, DELLAs are degraded and this then allows PIFs to promote elongation.<ref name="Zheng-2016">{{cite journal | vauthors = Zheng Y, Gao Z, Zhu Z | title = DELLA-PIF Modules: Old Dogs Learn New Tricks | language = English | journal = Trends in Plant Science | volume = 21 | issue = 10 | pages = 813–815 | date = October 2016 | pmid = 27569991 | doi = 10.1016/j.tplants.2016.08.006 | url = https://www.cell.com/trends/plant-science/fulltext/S1360-1385(16)30116-9 | url-access = subscription }}</ref> It was later found that DELLAs repress a large number of other transcription factors, among which are positive regulators of [[auxin]], [[brassinosteroid]] and [[ethylene]] signalling.<ref>{{cite journal | vauthors = Oh E, Zhu JY, Bai MY, Arenhart RA, Sun Y, Wang ZY | title = Cell elongation is regulated through a central circuit of interacting transcription factors in the Arabidopsis hypocotyl | journal = eLife | volume = 3 | date = May 2014 | pmid = 24867218 | pmc = 4075450 | doi = 10.7554/eLife.03031 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Marín-de la Rosa N, Sotillo B, Miskolczi P, Gibbs DJ, Vicente J, Carbonero P, Oñate-Sánchez L, Holdsworth MJ, Bhalerao R, Alabadí D, Blázquez MA | title = Large-scale identification of gibberellin-related transcription factors defines group VII ETHYLENE RESPONSE FACTORS as functional DELLA partners | journal = Plant Physiology | volume = 166 | issue = 2 | pages = 1022–32 | date = October 2014 | pmid = 25118255 | pmc = 4213073 | doi = 10.1104/pp.114.244723 }}</ref> DELLAs can repress transcription factors either by stopping their binding to DNA or by promoting their degradation.<ref name="Zheng-2016" />

==== Prefoldins and microtubule assembly ====
In addition to repressing transcription factors, DELLAs also bind to prefoldins (PFDs). PFDs are molecular [[Chaperone (protein)|chaperones]] (they assist in the folding of other proteins) that work in the [[cytosol]], but when DELLAs bind to them are restricted to the [[Cell nucleus|nucleus]]. An important function of PFDs is to assist in the folding of [[Tubulin|β-tubulin]], a vital component of the [[cytoskeleton]] in the form of [[microtubule]]s. As such, in the absence of Gibberellins (high level of DELLA proteins), PFDs reduce its activity, leading to a lower cellular pool of β-tubulin. When GA is present the DELLAs are degraded, PFDs can move to the cytosol and assist in the folding of β-tubulin. As such, GA allows for re-organisation of the cytoskeleton, and the elongation of cells.<ref>{{cite journal | vauthors = Locascio A, Blázquez MA, Alabadí D | title = Dynamic regulation of cortical microtubule organization through prefoldin-DELLA interaction | language = English | journal = Current Biology | volume = 23 | issue = 9 | pages = 804–9 | date = May 2013 | pmid = 23583555 | doi = 10.1016/j.cub.2013.03.053 | doi-access = free | bibcode = 2013CBio...23..804L | hdl = 10251/66422 | hdl-access = free }}</ref>

Microtubules are also required for the trafficking of [[Membrane vesicle trafficking|membrane vesicles]], that is needed for the correct positioning of several [[Transport protein|hormone transporters]]. One of the most well characterized hormone transporters are [[PIN proteins]], which are responsible for the movement of the hormone auxin between cells. In the absence of Gibberellins, DELLA proteins reduce the levels of microtubules and thereby inhibit membrane vesicle trafficking. This reduces the level of PIN proteins at the [[cell membrane]], and the level of auxin in the cell. GA reverses this process and allows for PIN protein trafficking to the cell membrane to enhance the level of auxin in the cell.<ref>{{cite journal | vauthors = Salanenka Y, Verstraeten I, Löfke C, Tabata K, Naramoto S, Glanc M, Friml J | title = Gibberellin DELLA signaling targets the retromer complex to redirect protein trafficking to the plasma membrane | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 115 | issue = 14 | pages = 3716–3721 | date = April 2018 | pmid = 29463731 | pmc = 5889667 | doi = 10.1073/pnas.1721760115 | doi-access = free | bibcode = 2018PNAS..115.3716S }}</ref>

== References ==
{{reflist|32em}}

== External links ==
* {{PPDB|1671}}

{{Plant hormones}}

{{Authority control}}

[[Category:Plant hormones]]
[[Category:Agronomy]]
[[Category:Diterpenes]]
[[Category:Aging-related substances in plants]]