The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase.
The monocytic leukemia zinc finger protein (MOZ) gene is rearranged in t(8;16)(p11;p13), t(8;22)(p11;q13) and inv(8)(p11q13) associated with acute myeloid leukemia. The other fusion partners involved are CBP, p300 and TIF2, transcriptional coactivators with known or potential histone acetyltransferase (HAT) activity. MOZ itself is a 2004-residue protein containing a putative acetyl CoA-binding motif, so it was hypothesized that MOZ is a HAT. Here we present direct evidence that MOZ has intrinsic HAT activity. Moreover, MOZ possesses a transcriptional repression domain at its N-terminal part and an activation domain at its C-terminal part. The activation domain does not show sequence similarity to any yeast proteins, but when tethered, it is able to activate transcription in yeast. Therefore, MOZ is a HAT with characteristics of a transcriptional coregulator, supporting the hypothesis that aberrant acetylation by abnormal MOZ proteins leads to leukemogenesis.
Champagne
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Molecular Oncology Group, Department of Medicine, McGill University Health Centre, Montréal, Québec H3A 1A1, Canada.
Pelletier
N
N
Yang
X J
XJ
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017930:Genes, Reporter; D051548:Histone Acetyltransferases; D058619:Maltose-Binding Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016335:Zinc Fingers
D002352:Carrier Proteins; D058619:Maltose-Binding Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human