DNA recognition by the aberrant retinoic acid receptors implicated in human acute promyelocytic leukemia

H. Hauksdóttir, M. L. Privalsky

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Human acute promyelocytic leukemias (APLs) are associated with chromosomal translocations that replace the NH2 terminus of wild-type retinoic acid receptor (RAR) α with portions of the promyelocytic leukemia protein (PML) or promyelocytic leukemia zinc-finger protein (PLZF). The wild-type RARα 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-RARα and PLZF-RARα 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 RXRα/RARα heterodimer, which is presumed to be the dominant receptor species in normal cells, differs from that of the PML-RARα and PLZF-RARα homodimers, which are thought to prevail in the oncogenic cell. We suggest that differences in target gene recognition by the normal and oncogenic RARα proteins may contribute to the leukemogenic phenotype.

Original languageEnglish (US)
Pages (from-to)85-98
Number of pages14
JournalCell Growth and Differentiation
Volume12
Issue number2
StatePublished - 2001

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Acute Promyelocytic Leukemia
Retinoic Acid Receptors
DNA
Retinoid X Receptors
Zinc Fingers
Leukemia
Proteins
Genetic Translocation
Oncogene Proteins
Retinoids
Phenotype

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

DNA recognition by the aberrant retinoic acid receptors implicated in human acute promyelocytic leukemia. / Hauksdóttir, H.; Privalsky, M. L.

In: Cell Growth and Differentiation, Vol. 12, No. 2, 2001, p. 85-98.

Research output: Contribution to journalArticle

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