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Cell growth
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====Linking Cdr2 to Wee1==== The protein kinase [[CDR2 (gene)|Cdr2]] (which negatively regulates Wee1) and the Cdr2-related kinase [[CDR1 (gene)|Cdr1]] (which directly phosphorylates and inhibits Wee1 ''in vitro'')<ref>{{cite journal |vauthors=Wu L, Russell P |title=Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase |journal=Nature |volume=363 |issue=6431 |pages=738β41 |date=June 1993 |pmid=8515818 |doi=10.1038/363738a0|bibcode = 1993Natur.363..738W |s2cid=4320080 }}</ref> are localized to a band of cortical nodes in the middle of interphase cells. After entry into mitosis, cytokinesis factors such as [[myosin II]] are recruited to similar nodes; these nodes eventually condense to form the [[cytokinesis|cytokinetic]] ring.<ref>{{cite journal |doi=10.1016/S1534-5807(03)00324-1 |vauthors=Wu JQ, Kuhn JR, Kovar DR, Pollard TD |title=Spatial and temporal pathway for assembly and constriction of the contractile ring in fission yeast cytokinesis |journal=Dev. Cell |volume=5 |issue=5 |pages=723β34 |date=November 2003 |pmid=14602073 |doi-access=free }}</ref> A previously uncharacterized protein, [[leukotriene B4 receptor|Blt1]], was found to colocalize with Cdr2 in the medial interphase nodes. Blt1 knockout cells had increased length at division, which is consistent with a delay in mitotic entry. This finding connects a physical location, a band of cortical nodes, with factors that have been shown to directly regulate mitotic entry, namely Cdr1, Cdr2, and Blt1. Further experimentation with [[green fluorescent protein|GFP]]-tagged proteins and mutant proteins indicates that the medial cortical nodes are formed by the ordered, Cdr2-dependent assembly of multiple interacting proteins during interphase. Cdr2 is at the top of this hierarchy and works upstream of Cdr1 and Blt1.<ref name=Moseley09>{{cite journal |vauthors=Moseley JB, Mayeux A, Paoletti A, Nurse P |title=A spatial gradient coordinates cell size and mitotic entry in fission yeast |journal=Nature |volume=459 |issue=7248 |pages=857β60 |date=June 2009 |pmid=19474789 |doi=10.1038/nature08074 |bibcode=2009Natur.459..857M|s2cid=4330336 }}</ref> Mitosis is promoted by the negative regulation of Wee1 by Cdr2. It has also been shown that Cdr2 recruits Wee1 to the medial cortical node. The mechanism of this recruitment has yet to be discovered. A Cdr2 kinase mutant, which is able to localize properly despite a loss of function in phosphorylation, disrupts the recruitment of Wee1 to the medial cortex and delays entry into mitosis. Thus, Wee1 localizes with its inhibitory network, which demonstrates that mitosis is controlled through Cdr2-dependent negative regulation of Wee1 at the medial cortical nodes.<ref name=Moseley09/>
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