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Acetylation and MAPK phosphorylation cooperate to regulate the degradation of active GATA-1.

ABSTRACT: Regulation of transcription requires mechanisms to both activate and terminate transcription factor activity. GATA-1 is a key haemopoietic transcription factor whose activity is increased by acetylation. We show here that acetylated GATA-1 is targeted for degradation via the ubiquitin/proteasome pathway. Acetylation positively signals ubiquitination, suggesting that activation by acetylation simultaneously marks GATA-1 for degradation. Promoter-specific MAPK phosphorylation then cooperates with acetylation to execute protein loss. The requirement for both modifications is novel and suggests a way by which degradation of the active protein can be specifically regulated in response to external phosphorylation-mediated signalling. As many transcription factors are activated by acetylation, we suggest that this might be a general mechanism to control transcription factor activity.

SUBMITTER: Hernandez-Hernandez A

PROVIDER: S-EPMC1523174 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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Acetylation and MAPK phosphorylation cooperate to regulate the degradation of active GATA-1.

Hernandez-Hernandez Angel A Ray Pampa P Litos Gabi G Ciro Marco M Ottolenghi Sergio S Beug Hartmut H Boyes Joan J

The EMBO journal 20060706 14

Regulation of transcription requires mechanisms to both activate and terminate transcription factor activity. GATA-1 is a key haemopoietic transcription factor whose activity is increased by acetylation. We show here that acetylated GATA-1 is targeted for degradation via the ubiquitin/proteasome pathway. Acetylation positively signals ubiquitination, suggesting that activation by acetylation simultaneously marks GATA-1 for degradation. Promoter-specific MAPK phosphorylation then cooperates with ...[more]

PMID: 16858405

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