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Article

  • The EMBO Journal (2006) 25, 3264 - 3274
  • doi:10.1038/sj.emboj.7601228

Published online: 6 July 2006

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

Angel Hernandez-Hernandez1,a, Pampa Ray1,bc, Gabi Litos2,c, Marco Ciro1,3,cd, Sergio Ottolenghi3,c, Hartmut Beug2,c and Joan Boyes1,4

  1. Section of Gene Function and Regulation, Institute of Cancer Research, London, UK
  2. Institute of Molecular Pathology, Vienna, Austria
  3. Department of Biotechnology and Bioscience, University of Milan-Bicocca, Milan, Italy
  4. Institute of Molecular and Cellular Biology, University of Leeds, Leeds, UK

Correspondence to:

Joan Boyes, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK. Tel.: +44 113 343 3147; Fax: +44 113 343 3167; E-mail: J.M.Boyes@leeds.ac.uk

aPresent address: Department of Biochemistry, University of Salamanca, Salamanca, Spain

bPresent address: Laboratory of Cell Biochemistry and Biology, NIH/NIDDK, Bethesda, MD, USA

cThese authors contributed equally to this work

dPresent address: European Institute of Oncology, Milan, Italy

Received 18 May 2006; Accepted 14 June 2006

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.

  • Keywords:

    • acetylation,
    • haemopoiesis,
    • phosphorylation,
    • transcription,
    • ubiquitination