Brief Communication abstract


Nature Cell Biology 3, 325 - 330 (2001)
Published online: 16 February 2001 | doi:10.1038/35060131

ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation

Hasem Habelhah1, Kavita Shah2, Lan Huang3, Antje Ostareck-Lederer4, A. L. Burlingame3, Kevan M. Shokat2, Matthias W. Hentze4 & Ze'ev Ronai1

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Heterogeneous nuclear ribonucleoprotein K (hnRNP-K) is one of a family of 20 proteins that are involved in transcription and post-transcriptional messenger RNA metabolism. The mechanisms that underlie regulation of hnRNP-K activities remain largely unknown. Here we show that cytoplasmic accumulation of hnRNP-K is phosphorylation-dependent. Mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) efficiently phosphorylates hnRNP-K both in vitro and in vivo at serines 284 and 353. Serum stimulation or constitutive activation of ERK kinase (MEK1) results in phosphorylation and cytoplasmic accumulation of hnRNP-K. Mutation at ERK phosphoacceptor sites in hnRNP-K abolishes the ability to accumulate in the cytoplasm and renders the protein incapable of regulating translation of mRNAs that have a differentiation-control element (DICE) in the 3' untranslated region (UTR). Similarly, treatment with a pharmacological inhibitor of the ERK pathway abolishes cytoplasmic accumulation of hnRNP-K and attenuates inhibition of mRNA translation. Our results establish the role of MAPK/ERK in phosphorylation-dependent cellular localization of hnRNP-K, which is required for its ability to silence mRNA translation.

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  1. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA
  2. Department of Cellular and Molecular Pharmacology, University of California at San Francisco, California 94143, USA
  3. Department of Pharmaceutical Chemistry, University of California at San Francisco, California 94143, USA
  4. Gene Expression Program, European Molecular Biology Laboratory, Heidelberg, D-69117, Germany

Correspondence to: Ze'ev Ronai1 e-mail: zeev.ronai@mssm.edu




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