Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6.
Many transcription factors function by repressing gene transcription. For a variety of these transcription factors the ability to physically recruit auxiliary proteins, denoted corepressors, is crucial for the ability to silence gene expression. We and others have previously implicated the SMRT corepressor in the actions of the PLZF transcription factor and in the function of its oncogenic derivative, PLZF-retinoic acid receptor (RARalpha), in promyelocytic leukemia. We report here that PLZF, and a structurally similar transcriptional repressor, BCL-6, can interact with a variety of corepressor proteins in addition to SMRT, including the mSin3A protein and (for PLZF) histone deacetylase-1. Unexpectedly, these additional interactions with corepressor components are nonequivalent for these otherwise similar oncoproteins, suggesting that transcriptional repression by BCL-6 and by PLZF may differ in mechanism. Furthermore, we demonstrate that the oncogenic PLZF-RARalpha chimera lacks several important corepressor interaction sites that are present in the native PLZF protein. Thus the t(11;17) translocation that creates the PLZF-RARalpha chimera generates an oncoprotein with potentially novel regulatory properties distinct from those of either parental protein. Our results demonstrate that otherwise similar transcription factors can differ notably in their interactions with the corepressor machinery.
Section of Microbiology, Division of Biological Sciences, University of California, Davis, California 95616, USA.
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D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D056985:Nuclear Receptor Co-Repressor 2; D010446:Peptide Fragments / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D010446:Peptide Fragments; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D014157:Transcription Factors; C092037:ZBTB16 protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex