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
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.
- Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA
- Department of Cellular and Molecular Pharmacology, University of California at San Francisco, California 94143, USA
- Department of Pharmaceutical Chemistry, University of California at San Francisco, California 94143, USA
- Gene Expression Program, European Molecular Biology Laboratory, Heidelberg, D-69117, Germany
Correspondence to: Ze'ev Ronai1 e-mail: zeev.ronai@mssm.edu
