Inhibition of CBP-Mediated Protein Acetylation by the Ets Family Oncoprotein PU.1

AUTOR(ES)

Hong, Wei

FONTE

American Society for Microbiology

RESUMO

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.

Documentos Relacionados

• CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing
• The Kaposi's Sarcoma-Associated Herpesvirus K8 Protein Interacts with CREB-Binding Protein (CBP) and Represses CBP-Mediated Transcription
• The Ets-related transcription factor PU.1 immortalizes erythroblasts.
• p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2
• Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ–CBP fusion protein