Rheb inhibits protein synthesis by activating the PERK-eIF2α signaling cascade

Richa Tyagi, Neelam Shahani, Lindsay Gorgen, Max Ferretti, William Pryor, Po Yu Chen, Supriya Swarnkar, Paul F. Worley, Katrin Karbstein, Solomon H. Snyder, Srinivasa Subramaniam

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Rheb, a ubiquitous small GTPase, is well known to bind and activate mTOR, which augments protein synthesis. Inhibition of protein synthesis is also physiologically regulated. Thus, with cell stress, the unfolded protein response system leads to phosphorylation of the initiation factor eIF2α and arrest of protein synthesis. We now demonstrate a major role for Rheb in inhibiting protein synthesis by enhancing the phosphorylation of eIF2α by protein kinase-like ER kinase (PERK). Interplay between the stimulatory and inhibitory roles of Rheb may enable cells to modulate protein synthesis in response to varying environmental stresses.

Original languageEnglish (US)
Pages (from-to)684-693
Number of pages10
JournalCell Reports
Issue number5
StatePublished - Feb 10 2015

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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