Whi2

Whi2 or Whiskey 2 is a 55 kDa globular,[1] scaffold protein located to cell periphery[2] 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.[3] Whi2p shares a conserved BTB structure domain to the family of human potassium channel tetramerization domain proteins (KCTDs).[4] KCTD family members have been associated with several type of cancers and epilepsy disorders.

Functional mechanism

Upon complexing with plasma membrane associated phosphatase Psr1 and Psr2, Whi2 induces general stress response by dephosphorylating general stress response transcription factor Msn2.[5] Whi2 is essential for Msn2 activity, moreover activation by Whi2 is dominant and independent of the PKA and TOR activation pathways.[6] Additionally, experiments suggests Whi2 plays a role in Ras2 deactivation or degradation during nutrient depletion.[7] Whi2-Psr1/Psr2 complex is also required for inhibition of TORC1 activity under conditions of nutrient deprivation.[8] 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.[9][4] 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.[10]

References
  1. "Protein Overview: WHI2". YeastRC.org. Retrieved 17 April 2012.
  2. Yofe, Ido; Weill, Uri; Meurer, Matthias; Chuartzman, Silvia; Zalckvar, Einat; Goldman, Omer; Ben-Dor, Shifra; Schütze, Conny; Wiedemann, Nils; Knop, Michael; Khmelinskii, Anton; Schuldiner, Maya (April 2016). "One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy". Nature Methods. 13 (4): 371–378. doi:10.1038/nmeth.3795. ISSN 1548-7091. PMC 4869835. PMID 26928762.
  3. "WHI2 Summary". YeastGenome.org. Retrieved 4 January 2012.
  4. Teng, Xinchen; Dayhoff-Brannigan, Margaret; Cheng, Wen-Chih; Gilbert, Catherine E.; Sing, Cierra N.; Diny, Nicola L.; Wheelan, Sarah J.; Dunham, Maitreya J.; Boeke, Jef D.; Pineda, Fernando J.; Hardwick, J. Marie (December 2013). "Genome-wide Consequences of Deleting Any Single Gene". Molecular Cell. 52 (4): 485–494. doi:10.1016/j.molcel.2013.09.026. ISSN 1097-2765. PMC 3975072. PMID 24211263.
  5. Kaida, D; Yashiroda, H; Toh-e, A; Kikuchi, Y (2002). "Yeast Whi2 and Psr1-phosphatase form a complex and regulate STRE-mediated gene expression". Genes to Cells. 7 (6): 543–52. doi:10.1046/j.1365-2443.2002.00538.x. PMID 12090248.
  6. Sadeh, Amit; Movshovich, Natalia; Volokh, Misha; Gheber, Larisa; Aharoni, Amir (2011). "Fine-tuning of the Msn2/4-mediated yeast stress responses as revealed by systematic deletion of Msn2/4 partners". Molecular Biology of the Cell. 22 (17): 3127–38. doi:10.1091/mbc.E10-12-1007. PMC 3164460. PMID 21757539.
  7. Müller, Matthias; Reichert, Andreas S. (2011). "Mitophagy, mitochondrial dynamics and the general stress response in yeast". Biochemical Society Transactions. 39 (5): 1514–9. doi:10.1042/BST0391514. PMID 21936844.
  8. Teng, Xinchen; Hardwick, J. Marie (2019-01-30). "Whi2: a new player in amino acid sensing". Current Genetics. 65 (3): 701–709. doi:10.1007/s00294-018-00929-9. ISSN 0172-8083. PMID 30701278. S2CID 253819083.
  9. Comyn, Sophie A.; Flibotte, Stéphane; Mayor, Thibault (2017-06-23). "Recurrent background mutations in WHI2 impair proteostasis and degradation of misfolded cytosolic proteins in Saccharomyces cerevisiae". Scientific Reports. 7 (1): 4183. Bibcode:2017NatSR...7.4183C. doi:10.1038/s41598-017-04525-8. ISSN 2045-2322. PMC 5482819. PMID 28646136.
  10. Maršíková, Jana; Pavlíčková, Martina; Wilkinson, Derek; Váchová, Libuše; Hlaváček, Otakar; Hatáková, Ladislava; Palková, Zdena (2020-06-15). "The Whi2p-Psr1p/Psr2p complex regulates interference competition and expansion of cells with competitive advantage in yeast colonies". Proceedings of the National Academy of Sciences. 117 (26): 15123–15131. Bibcode:2020PNAS..11715123M. doi:10.1073/pnas.1922076117. ISSN 0027-8424. PMID 32541056.
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