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 language||English (US)|
|Number of pages||14|
|Journal||Cell Growth and Differentiation|
|State||Published - 2001|
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology