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