Whi2 is a conserved negative regulator of TORC1 in response to low amino acids

PLoS Genetics
Xianghui ChenXinchen Teng

Abstract

Yeast WHI2 was originally identified in a genetic screen for regulators of cell cycle arrest and later suggested to function in general stress responses. However, the function of Whi2 is unknown. Whi2 has predicted structure and sequence similarity to human KCTD family proteins, which have been implicated in several cancers and are causally associated with neurological disorders but are largely uncharacterized. The identification of conserved functions between these yeast and human proteins may provide insight into disease mechanisms. We report that yeast WHI2 is a new negative regulator of TORC1 required to suppress TORC1 activity and cell growth specifically in response to low amino acids. In contrast to current opinion, WHI2 is dispensable for TORC1 inhibition in low glucose. The only widely conserved mechanism that actively suppresses both yeast and mammalian TORC1 specifically in response to low amino acids is the conserved SEACIT/GATOR1 complex that inactivates the TORC1-activating RAG-like GTPases. Unexpectedly, Whi2 acts independently and simultaneously with these established GATOR1-like Npr2-Npr3-Iml1 and RAG-like Gtr1-Gtr2 complexes, and also acts independently of the PKA pathway. Instead, Whi2 inhibits TORC1 activity...Continue Reading

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Citations

Feb 1, 2019·Current Genetics·Xinchen Teng, J Marie Hardwick
Aug 31, 2018·FEMS Yeast Research·Xinchen TengJ Marie Hardwick
Feb 11, 2020·Frontiers in Microbiology·A Pedro GonçalvesN Louise Glass
Jun 15, 2019·CNS Neuroscience & Therapeutics·Xinchen TengJ Marie Hardwick
Jun 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jana MaršíkováZdena Palková
Jan 21, 2019·Biochemical Pharmacology·Madhura KulkarniJ Marie Hardwick

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Methods Mentioned

BETA
environmental stresses
GTPases
GTPase
pull-down
PCR

Software Mentioned

ImageJ
SEACIT
Gtr

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