RXR is an essential component of the oncogenic PML/RARA complex in vivo.

Published

Journal Article

Although PML-enforced RARA homodimerization allows PML/RARA to bind DNA independently of its coreceptor RXR, the latter was identified within the PML/RARA complex. We demonstrate that a PML/RARA mutant defective for RXR binding fails to trigger APL development in transgenic mice, although it still transforms primary hematopoietic progenitors ex vivo. RXR enhances PML/RARA binding to DNA and is required for rexinoid-induced APL differentiation. In RA-treated PML/RARA-transformed cells, the absence of RXR binding results in monocytic, rather than granulocytic, differentiation. PML/RARA enhances posttranslational modifications of RXRA, including its sumoylation, suggesting that PML-bound sumoylation enzymes target RXRA and possibly other PML/RARA-bound chromatin proteins, further contributing to deregulated transcription. Thus, unexpectedly, RXR contributes to several critical aspects of in vivo transformation.

Full Text

Duke Authors

Cited Authors

  • Zhu, J; Nasr, R; Pérès, L; Riaucoux-Lormière, F; Honoré, N; Berthier, C; Kamashev, D; Zhou, J; Vitoux, D; Lavau, C; de Thé, H

Published Date

  • July 2007

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 23 - 35

PubMed ID

  • 17613434

Pubmed Central ID

  • 17613434

International Standard Serial Number (ISSN)

  • 1535-6108

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2007.06.004

Language

  • eng

Conference Location

  • United States