Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP.

摘要: Evi-1 is a transcription factor that implicated in leukemic transformation of hematopoietic cells. Two distinct alternative forms, Evi-1a and Evi-1c, are generated from the EVI-1 gene. Whereas widely recognized as an oncoprotein, role for which has additional PR domain amino-terminus Evi-1a, leukemogenesis, not been elucidated thus far. Aberrant oligomerization factors recently emerged prevalent mechanism activating their oncogenic potential malignancies. Here, to study mechanisms underlie Evi-1-mediated oncogenesis, we investigated formation oligomeric complexes by proteins. We show forms homo-oligomers, whereas Evi-1c exclusively exists monomer mammalian Remarkably, lost ability interact with CtBP, transcriptional corepressor associates Evi-1a. As consequence, repress transforming growth factor-β (TGF-β) signaling significantly abrogated. These results identify novel function regulate suggest homo-oligomerization may play critical recruitment In addition, found chimeric oncoprotein acute myelocytic leukemia (AML)1-Evi-1, t(3;21) leukemia, also homo-oligomers hetero-oligomers while it did Evi-1c. Consistent results, repression TGF-β AML1-Evi-1 was enhanced hardly affected presence contribute Evi-1-containing