Inhibition of CBP-mediated protein acetylation by the Ets family oncoprotein PU.1

Wei Hong, Alexander Y. Kim, Sokun Ky, Carrie Rakowski, Sang Beom Seo, Debabrata Chakravarti, Michael Atchison, Gerd A. Blobel*

*Corresponding author for this work

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Aberrant expression of PU.1 inhibits erythroid cell differentiation and contributes to the formation of murine erythroleukemias (MEL). The molecular mechanism by which this occurs is poorly understood. Here we show that PU.1 specifically and efficiently inhibits CBP-mediated acetylation of several nuclear proteins, including the hematopoietic transcription factors GATA-1, NF-E2, and erythroid Krüppel-like factor. In addition, PU.1 blocks acetylation of histones and interferes with acetylation-dependent transcriptional events. CBP acetyltransferase activity increases during MEL cell differentiation as PU.1 levels decline and is inhibited by sustained PU.1 expression. Finally, PU.1 inhibits the differentiation-associated increase in histone acetylation at an erythroid-specific gene locus in vivo. Together, these findings suggest that aberrant expression of PU.1 and possibly other members of the Ets family of oncoproteins subverts normal cellular differentiation in part by inhibiting the acetylation of critical nuclear factors involved in balancing cellular proliferation and maturation.

Original languageEnglish (US)
Pages (from-to)3729-3743
Number of pages15
JournalMolecular and cellular biology
Volume22
Issue number11
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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