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[edit]
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[edit]
- ^ "Protein Overview: WHI2". YeastRC.org. Retrieved 17 April 2012.
- ^ 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.
- ^ "WHI2 Summary". YeastGenome.org. Retrieved 4 January 2012.
- ^ a b 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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. PMC 7334569. PMID 32541056.