Literature DB >> 15620355

TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1.

Dietmar E Martin1, Alexandre Soulard, Michael N Hall.   

Abstract

The regulation of ribosome biogenesis in response to environmental conditions is a key aspect of cell growth control. Ribosomal protein (RP) genes are regulated by the nutrient-sensitive, conserved target of rapamycin (TOR) signaling pathway. TOR controls the subcellular localization of protein kinase A (PKA) and the PKA-regulated kinase YAK1. However, the target transcription factor(s) of the TOR-PKA pathway are unknown. We show that regulation of RP gene transcription via TOR and PKA in yeast involves the Forkhead-like transcription factor FHL1 and the two cofactors IFH1 (a coactivator) and CRF1 (a corepressor). TOR, via PKA, negatively regulates YAK1 and maintains CRF1 in the cytoplasm. Upon TOR inactivation, activated YAK1 phosphorylates and activates CRF1. Phosphorylated CRF1 accumulates in the nucleus and competes with IFH1 for binding to FHL1 at RP gene promoters, and thereby inhibits transcription of RP genes. Thus, we describe a signaling mechanism linking an environmental sensor to ribosome biogenesis.

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Year:  2004        PMID: 15620355     DOI: 10.1016/j.cell.2004.11.047

Source DB:  PubMed          Journal:  Cell        ISSN: 0092-8674            Impact factor:   41.582


  212 in total

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