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Transcription factor
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=== Functional === Transcription factors have been classified according to their regulatory function:<ref name="pmid11823631" /> * I. '''Constitutive''' β present in all cells at all times, constantly active, all being [[Activator (genetics)|activators]]. Very likely playing an important facilitating role in the transcription of many chromosomal genes, possibly in genes that seem to be always transcribed (e.g., structural proteins like tubulin and actin, and ubiquitous metabolic enzymes such as glyceraldehyde phosphate dehydrogenase (GAPDH)). E.g.: [[general transcription factor]]s, [[Sp1 transcription factor|Sp1]], [[Nuclear factor 1|NF1]], [[Ccaat-enhancer-binding proteins|CCAAT]] * II. '''Regulatory (conditionally active)''' β require activation. ** II.A '''Developmental''' '''(cell-type specific)''' β beginning in a fertilized egg. Once expressed, require no additional activation. E.g.:[[GATA transcription factor|GATA]], [[hepatocyte nuclear factors|HNF]], [[PIT-1]], [[MyoD]], [[Myf5]], [[Hox (gene)|Hox]], [[winged-helix transcription factors|Winged Helix]] ** II.B '''Signal-dependent''' β may be either developmentally restricted in their expression or present in most or all cells, but all are inactive (or minimally active) until cells containing such proteins are exposed to the appropriate intra- or extracellular signal. *** II.B.1 '''Extracellular ligand ([[endocrine system|endocrine]] or [[paracrine signalling|paracrine]])-dependent''' β [[nuclear receptor]]s. *** II.B.2 '''Intracellular ligand ([[autocrine signalling|autocrine]])-dependent''' β activated by small intracellular molecules. E.g.: [[Sterol regulatory element binding protein|SREBP]], [[p53]], orphan nuclear receptors. *** II.B.3 '''Cell surface receptor-ligand interaction-dependent''' β activated by second messenger signaling cascades. **** II.B.3.a Constitutive nuclear factors activated by serine phosphorylation β residing within the nucleus. The serine phosphorylation enzymes can be activated by two main routes: ***** [[G protein-coupled receptor|G protein-coupled receptors]] upon ligand binding increase intracellular levels of [[Second messenger system|second messengers]] ([[Cyclic adenosine monophosphate|cAMP]], [[Inositol trisphosphate|IP<sub>3</sub>]], [[Diglyceride|DAG]], calcium) which, in turn, activate protein [[serine-threonine kinase]] enzymes (such as [[Protein kinase A|PKA]], [[Protein kinase C|PKC]]). ***** [[Receptor tyrosine kinase|Receptor tyrosine kinases]] upon ligand binding trigger other pathways that finally terminate in serine phosphorylation of the abundant resident nuclear transcription factors. ***** Examples include: [[CREB]], [[AP-1 (transcription factor)|AP-1]], [[Mef2]] **** II.B.3.b '''Latent cytoplasmic factors''' β residing in the cytoplasm when inactive. Structurally and chemically very diverse group, and so are their activation pathways. E.g.: [[STAT protein|STAT]], [[R-SMAD]], [[NF-ΞΊB]], [[Notch signaling|Notch]], [[Tubby protein|TUBBY]], [[NFAT]]
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