DNA Recognition by the Aberrant Retinoic Acid Receptors Implicated in Human Acute Promyelocytic Leukemia

Overview

Journal Cell Growth Differ

Specialties Cell Biology
Molecular Biology

Date 2001 Mar 13

PMID 11243468

Citations 14

Authors

H Hauksdottir

M L Privalsky

Affiliations

Soon will be listed here.

Abstract

Human acute promyelocytic leukemias (APLs) are associated with chromosomal translocations that replace the NH2 terminus of wild-type retinoic acid receptor (RAR) alpha with portions of the promyelocytic leukemia protein (PML) or promyelocytic leukemia zinc-finger protein (PLZF). The wild-type RARalpha readily forms heterodimers with the retinoid X receptors (RXRs), and these RAR/RXR heterodimers appear to be the principal mediators of retinoid signaling in normal cells. In contrast, PML-RARalpha and PLZF-RARa display an enhanced ability to form homodimers, and this enhanced homodimer formation is believed to contribute to the neoplastic properties of these chimeric oncoproteins. We report here that the DNA recognition specificity of the RXRalpha/RARa heterodimer, which is presumed to be the dominant receptor species in normal cells, differs from that of the PML-RARalpha and PLZF-RARalpha homodimers, which are thought to prevail in the oncogenic cell. We suggest that differences in target gene recognition by the normal and oncogenic RARalpha proteins may contribute to the leukemogenic phenotype.

Citing Articles

Interaction with RXR is necessary for NPM-RAR-induced myeloid differentiation blockade.

Rush E, Pollock S, Abecassis I, Redner R Leuk Res. 2013; 37(12):1704-10.

PMID: 24183235 PMC: 3876950. DOI: 10.1016/j.leukres.2013.09.024.

Characterisation of genome-wide PLZF/RARA target genes.

Spicuglia S, Vincent-Fabert C, Benoukraf T, Tiberi G, Saurin A, Zacarias-Cabeza J PLoS One. 2011; 6(9):e24176.

PMID: 21949697 PMC: 3176768. DOI: 10.1371/journal.pone.0024176.

A mechanism for pituitary-resistance to thyroid hormone (PRTH) syndrome: a loss in cooperative coactivator contacts by thyroid hormone receptor (TR)beta2.

Lee S, Young B, Wan W, Chan I, Privalsky M Mol Endocrinol. 2011; 25(7):1111-25.

PMID: 21622532 PMC: 3125096. DOI: 10.1210/me.2010-0448.

Aberrant corepressor interactions implicated in PML-RAR(alpha) and PLZF-RAR(alpha) leukemogenesis reflect an altered recruitment and release of specific NCoR and SMRT splice variants.

Mengeling B, Phan T, Goodson M, Privalsky M J Biol Chem. 2010; 286(6):4236-47.

PMID: 21131350 PMC: 3039402. DOI: 10.1074/jbc.M110.200964.

Estrogen receptors recruit SMRT and N-CoR corepressors through newly recognized contacts between the corepressor N terminus and the receptor DNA binding domain.

Varlakhanova N, Snyder C, Jose S, Hahm J, Privalsky M Mol Cell Biol. 2010; 30(6):1434-45.

PMID: 20065040 PMC: 2832498. DOI: 10.1128/MCB.01002-09.

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