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The TOR-dependent phosphoproteome and regulation of cellular protein synthesis.

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journal contribution
posted on 20.08.2021, 10:34 by Tiffany Mak, Andrew W Jones, Paul Nurse
Cell growth is orchestrated by a number of interlinking cellular processes. Components of the TOR pathway have been proposed as potential regulators of cell growth, but little is known about their immediate effects on protein synthesis in response to TOR-dependent growth inhibition. Here, we present a resource providing an in-depth characterisation of Schizosaccharomyces pombe phosphoproteome in relation to changes observed in global cellular protein synthesis upon TOR inhibition. We find that after TOR inhibition, the rate of protein synthesis is rapidly reduced and that notable phosphorylation changes are observed in proteins involved in a range of cellular processes. We show that this reduction in protein synthesis rates upon TOR inhibition is not dependent on S6K activity, but is partially dependent on the S. pombe homologue of eIF4G, Tif471. Our study demonstrates the impact of TOR-dependent phospho-regulation on the rate of protein synthesis and establishes a foundational resource for further investigation of additional TOR-regulated targets both in fission yeast and other eukaryotes.

Funding

Crick (Grant ID: 10121, Grant title: Nurse FC001121) Wellcome Trust (Grant ID: 093917/C/10/A, Grant title: WT 093917/C/10/A) Wellcome Trust (Grant ID: 214183/Z/18/Z, Grant title: WT 214183/Z/18/Z)

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