Journal article
ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation
Nature cell biology, Vol.3(3), pp.325-330
03/2001
DOI: 10.1038/35060131
PMID: 11231586
Abstract
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.
Details
- Title: Subtitle
- ERK phosphorylation drives cytoplasmic accumulation of hnRNP-K and inhibition of mRNA translation
- Creators
- Kavita Shah - Department of Cellular and Molecular Pharmacology, University of California at San FranciscoKevan M Shokat - Department of Cellular and Molecular Pharmacology, University of California at San FranciscoHasem Habelhah - Ruttenberg Cancer Center, Mount Sinai School of MedicineLan Huang - Department of Pharmaceutical Chemistry, University of California at San FranciscoAntje Ostareck-Lederer - Gene Expression Program, European Molecular Biology LaboratoryMatthias W Hentze - Gene Expression Program, European Molecular Biology LaboratoryA. L Burlingame - Department of Pharmaceutical Chemistry, University of California at San FranciscoZe'ev Ronai - Ruttenberg Cancer Center, Mount Sinai School of Medicine
- Resource Type
- Journal article
- Publication Details
- Nature cell biology, Vol.3(3), pp.325-330
- DOI
- 10.1038/35060131
- PMID
- 11231586
- ISSN
- 1465-7392
- eISSN
- 1476-4679
- Language
- English
- Date published
- 03/2001
- Academic Unit
- Pathology
- Record Identifier
- 9984047613702771
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