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

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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Schmidlin, M., Lu, M., Leuenberger, S. A., Stoecklin, G., Mallaun, M., Gross, B., Gherzi, R., Hess, D., Hemmings, B. A., & Moroni, C. (2004). The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B. EMBO Journal, 23(24), 4760-4769. https://doi.org/10.1038/sj.emboj.7600477

The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B. / Schmidlin, Martin; Lu, Min; Leuenberger, Sabrina A.; Stoecklin, Georg; Mallaun, Michel; Gross, Brigitte; Gherzi, Roberto; Hess, Daniel; Hemmings, Brian A.; Moroni, Christoph.

In: EMBO Journal, Vol. 23, No. 24, 08.12.2004, p. 4760-4769.

Research output: Contribution to journal › Article

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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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AU - Mallaun, Michel

AU - Gross, Brigitte

AU - Gherzi, Roberto

AU - Hess, Daniel

AU - Hemmings, Brian A.

AU - Moroni, Christoph

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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.

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