Whi2
Whi2 or Whiskey 2 is a 55 kDa globular,{{cite web |title=Protein Overview: WHI2 |url=http://www.yeastrc.org/pdr/yeastProteinRedirect.do?acc=YOR043W#y2hData|work=YeastRC.org |accessdate=17 April 2012}} scaffold protein located to cell periphery{{Cite journal |last1=Yofe |first1=Ido |last2=Weill |first2=Uri |last3=Meurer |first3=Matthias |last4=Chuartzman |first4=Silvia |last5=Zalckvar |first5=Einat |last6=Goldman |first6=Omer |last7=Ben-Dor |first7=Shifra |last8=Schütze |first8=Conny |last9=Wiedemann |first9=Nils |last10=Knop |first10=Michael |last11=Khmelinskii |first11=Anton |last12=Schuldiner |first12=Maya |date=April 2016 |title=One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy |journal=Nature Methods |language=en |volume=13 |issue=4 |pages=371–378 |doi=10.1038/nmeth.3795 |issn=1548-7091 |pmc=4869835 |pmid=26928762}} in Saccharomyces cerevisiae, which plays an essential role in regulating stress response pathways, apparently by passing input signals about nutrient availability on to stress responsive elements and autophagy/mitophagy mechanisms. It is encoded by a 1.46 kbp gene located on chromosome 15.{{cite web |title=WHI2 Summary |url=https://www.yeastgenome.org/locus/S000005569 |work=YeastGenome.org |accessdate=4 January 2012}} Whi2p shares a conserved BTB structure domain to the family of human potassium channel tetramerization domain proteins (KCTDs).{{Cite journal |last1=Teng |first1=Xinchen |last2=Dayhoff-Brannigan |first2=Margaret |last3=Cheng |first3=Wen-Chih |last4=Gilbert |first4=Catherine E. |last5=Sing |first5=Cierra N. |last6=Diny |first6=Nicola L. |last7=Wheelan |first7=Sarah J. |last8=Dunham |first8=Maitreya J. |last9=Boeke |first9=Jef D. |last10=Pineda |first10=Fernando J. |last11=Hardwick |first11=J. Marie |date=December 2013 |title=Genome-wide Consequences of Deleting Any Single Gene |url=http://dx.doi.org/10.1016/j.molcel.2013.09.026 |journal=Molecular Cell |volume=52 |issue=4 |pages=485–494 |doi=10.1016/j.molcel.2013.09.026 |pmid=24211263 |pmc=3975072 |issn=1097-2765}} KCTD family members have been associated with several type of cancers and epilepsy disorders.
Functional mechanism
Upon complexing with plasma membrane associated phosphatase [https://www.yeastgenome.org/locus/S000003933 Psr1] and [https://www.yeastgenome.org/locus/S000004009 Psr2], Whi2 induces general stress response by dephosphorylating general stress response transcription factor Msn2.{{cite journal |pmid=12090248 |year=2002 |last1=Kaida |first1=D |last2=Yashiroda |first2=H |last3=Toh-e |first3=A |last4=Kikuchi |first4=Y |title=Yeast Whi2 and Psr1-phosphatase form a complex and regulate STRE-mediated gene expression |volume=7 |issue=6 |pages=543–52 |journal=Genes to Cells |doi=10.1046/j.1365-2443.2002.00538.x|doi-access=free }} Whi2 is essential for Msn2 activity, moreover activation by Whi2 is dominant and independent of the PKA and TOR activation pathways.{{cite journal |doi=10.1091/mbc.E10-12-1007 |title=Fine-tuning of the Msn2/4-mediated yeast stress responses as revealed by systematic deletion of Msn2/4 partners |year=2011 |last1=Sadeh |first1=Amit |last2=Movshovich |first2=Natalia |last3=Volokh |first3=Misha |last4=Gheber |first4=Larisa |last5=Aharoni |first5=Amir |journal=Molecular Biology of the Cell |volume=22 |issue=17 |pages=3127–38 |pmid=21757539 |pmc=3164460}} Additionally, experiments suggests Whi2 plays a role in Ras2 deactivation or degradation during nutrient depletion.{{cite journal |first1=Matthias |last1=Müller |first2=Andreas S. |last2=Reichert |journal=Biochemical Society Transactions |pmid=21936844 |year=2011 |title=Mitophagy, mitochondrial dynamics and the general stress response in yeast |volume=39 |issue=5 |pages=1514–9 |doi=10.1042/BST0391514}} Whi2-Psr1/Psr2 complex is also required for inhibition of TORC1 activity under conditions of nutrient deprivation.{{Cite journal |last1=Teng |first1=Xinchen |last2=Hardwick |first2=J. Marie |date=2019-01-30 |title=Whi2: a new player in amino acid sensing |url=http://dx.doi.org/10.1007/s00294-018-00929-9 |journal=Current Genetics |volume=65 |issue=3 |pages=701–709 |doi=10.1007/s00294-018-00929-9 |pmid=30701278 |s2cid=253819083 |issn=0172-8083|url-access=subscription }} Furthermore, a striking characteristic of Whi2 is the repeated observation of spontaneous mutations in the WHI2 gene in the yeast library of knock-out strains and in genome evolutionary studies.{{Cite journal |last1=Comyn |first1=Sophie A. |last2=Flibotte |first2=Stéphane |last3=Mayor |first3=Thibault |date=2017-06-23 |title=Recurrent background mutations in WHI2 impair proteostasis and degradation of misfolded cytosolic proteins in Saccharomyces cerevisiae |url= |journal=Scientific Reports |volume=7 |issue=1 |page=4183 |doi=10.1038/s41598-017-04525-8 |pmid=28646136 |issn=2045-2322|pmc=5482819 |bibcode=2017NatSR...7.4183C }} Recently a novel function of Whi2-Psr1/Psr2 complex identified in balancing cell population and regulating expansion of cells with fitness advantage in dense yeast populations.{{Cite journal |last1=Maršíková |first1=Jana |last2=Pavlíčková |first2=Martina |last3=Wilkinson |first3=Derek |last4=Váchová |first4=Libuše |last5=Hlaváček |first5=Otakar |last6=Hatáková |first6=Ladislava |last7=Palková |first7=Zdena |date=2020-06-15 |title=The Whi2p-Psr1p/Psr2p complex regulates interference competition and expansion of cells with competitive advantage in yeast colonies |journal=Proceedings of the National Academy of Sciences |volume=117 |issue=26 |pages=15123–15131 |doi=10.1073/pnas.1922076117 |pmid=32541056 |bibcode=2020PNAS..11715123M |issn=0027-8424 |doi-access=free |pmc=7334569 }}
References
{{reflist}}