The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B

Martin Schmidlin; Min Lu; Sabrina A. Leuenberger; Georg Stoecklin; Michel Mallaun; Brigitte Gross; Roberto Gherzi; Daniel Hess; Brian A. Hemmings; Christoph Moroni

doi:10.1038/sj.emboj.7600477

The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B

Martin Schmidlin, Min Lu, Sabrina A. Leuenberger, Georg Stoecklin, Michel Mallaun, Brigitte Gross, Roberto Gherzi, Daniel Hess, Brian A. Hemmings, Christoph Moroni

A.O.U. San Martino - IST, Istituto Nazionale Ricerca sul Cancro (GENOVA)

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	4760-4769
Number of pages	10
Journal	EMBO Journal
Volume	23
Issue number	24
DOIs	https://doi.org/10.1038/sj.emboj.7600477
Publication status	Published - Dec 8 2004

Keywords

Exosome
Insulin
mRNA turnover
PKB
Zinc-finger protein

ASJC Scopus subject areas

Genetics
Cell Biology

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10.1038/sj.emboj.7600477

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title = "The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B",

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.",

keywords = "Exosome, Insulin, mRNA turnover, PKB, Zinc-finger protein",

author = "Martin Schmidlin and Min Lu and Leuenberger, {Sabrina A.} and Georg Stoecklin and Michel Mallaun and Brigitte Gross and Roberto Gherzi and Daniel Hess and Hemmings, {Brian A.} and Christoph Moroni",

year = "2004",

month = dec,

day = "8",

doi = "10.1038/sj.emboj.7600477",

language = "English",

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T1 - The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B

AU - Schmidlin, Martin

AU - Lu, Min

AU - Leuenberger, Sabrina A.

AU - Stoecklin, Georg

AU - Mallaun, Michel

AU - Gross, Brigitte

AU - Gherzi, Roberto

AU - Hess, Daniel

AU - Hemmings, Brian A.

AU - Moroni, Christoph

PY - 2004/12/8

Y1 - 2004/12/8

N2 - 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.

AB - 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.

KW - Exosome

KW - Insulin

KW - mRNA turnover

KW - PKB

KW - Zinc-finger protein

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JO - EMBO Journal

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ER -

The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B

Abstract

Keywords

ASJC Scopus subject areas

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