ArticlePLoS genetics2018
Whi2 is a conserved negative regulator of TORC1 in response to low amino acids.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Time-resolved functional genomics using deep learning reveals global hierarchical control of autophagy.Nature cell biology · 2026Article
- Multilayered regulation of TORC1 signaling by Ait1, Gcn2, and SEAC/GATOR during nitrogen limitation and starvation.Nature communications · 2025Article
- The Whi2-Psr1-Psr2 complex selectively regulates TORC1 and autophagy under low leucine conditions but not nitrogen depletion.Autophagy · 2025Article
- Article
- Chromosome Segregation in Closed Mitosis Under an Excess of Nuclear Envelope.Biology of the cell · 2025Article
- Crosstalk between dysregulated amino acid sensing and glucose and lipid metabolism in colorectal cancer.Frontiers in oncology · 2025Review
- Enhancing probiotic impact: engineeringApplied and environmental microbiology · 2024Article
- Genetic effects on molecular network states explain complex traits.Molecular systems biology · 2023Article
- Effect of Amino Acids onFoods (Basel, Switzerland) · 2023Article
- TORC1 Signaling in Fungi: From Yeasts to Filamentous Fungi.Microorganisms · 2023Review
- Article
- Quiescence inAnnual review of genetics · 2022Review
- Article
- Gene loss and compensatory evolution promotes the emergence of morphological novelties in budding yeast.Nature ecology & evolution · 2022Article
- MoWhi2 Mediates Mitophagy to Regulate Conidiation and Pathogenesis inInternational journal of molecular sciences · 2022Article
- Yeast cell death pathway requiring AP-3 vesicle trafficking leads to vacuole/lysosome membrane permeabilization.Cell reports · 2022Article
- Effects of abolishing Whi2 on the proteome and nitrogen catabolite repression-sensitive protein production.G3 (Bethesda, Md.) · 2022Article
- Article
- Pib2 as an Emerging Master Regulator of Yeast TORC1.Biomolecules · 2021Review
- SEA and GATOR 10 Years Later.Cells · 2021Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
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 through its binding partners, protein phosphatases Psr1 and Psr2, which were previously thought to only regulate amino acid levels downstream of TORC1. Furthermore, the ability to suppress TORC1 is conserved in the SKP1/BTB/POZ domain-containing, Whi2-like human protein KCTD11 but not other KCTD family members tested.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.