The ARE-dependent MRNA-destabilizing Activity of BRF1 is Regulated by Protein Kinase B

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2004 Nov 13

PMID 15538381

Citations 68

Authors

Martin Schmidlin

Min Lu

Sabrina A Leuenberger

Georg Stoecklin

Michel Mallaun

Brigitte Gross

Roberto Gherzi

Daniel Hess

Brian A Hemmings

Christoph Moroni

Affiliations

Soon will be listed here.

Abstract

Butyrate response factor (BRF1) belongs to the Tis11 family of CCCH zinc-finger proteins, which bind to mRNAs containing an AU-rich element (ARE) in their 3' untranslated region and promote their deadenylation and rapid degradation. Independent signal transduction pathways have been reported to stabilize ARE-containing transcripts by a process thought to involve phosphorylation of ARE-binding proteins. Here we report that protein kinase B (PKB/Akt) stabilizes ARE transcripts by phosphorylating BRF1 at serine 92 (S92). Recombinant BRF1 promoted in vitro decay of ARE-containing mRNA (ARE-mRNA), yet phosphorylation by PKB impaired this activity. S92 phosphorylation of BRF1 did not impair ARE binding, but induced complex formation with the scaffold protein 14-3-3. In vivo and in vitro data support a model where PKB causes ARE-mRNA stabilization by inactivating BRF1 through binding to 14-3-3.

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