Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RAR∅, and BCL-6

Chi Wai Wong, Martin L. Privalsky

Research output: Contribution to journalArticlepeer-review

130 Scopus citations

Abstract

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 (RARα), 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- RARE 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-RARα 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.

Original languageEnglish (US)
Pages (from-to)27695-27702
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number42
DOIs
StatePublished - Oct 16 1998

ASJC Scopus subject areas

  • Biochemistry

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