TY - JOUR
T1 - Inhibition of CBP-mediated protein acetylation by the Ets family oncoprotein PU.1
AU - Hong, Wei
AU - Kim, Alexander Y.
AU - Ky, Sokun
AU - Rakowski, Carrie
AU - Seo, Sang Beom
AU - Chakravarti, Debabrata
AU - Atchison, Michael
AU - Blobel, Gerd A.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.22.11.3729-3743.2002
DO - 10.1128/MCB.22.11.3729-3743.2002
M3 - Article
C2 - 11997509
AN - SCOPUS:0036094806
SN - 0270-7306
VL - 22
SP - 3729
EP - 3743
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 11
ER -