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- Title
Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A.
- Authors
Yeyati, Patricia L; Shaknovich, Rita; Boterashvili, Sima; Li, Jia; Ball, Helen J; Waxman, Samuel; Nason-Burchenal, Kathryn; Dmitrovsky, Ethan; Zelent, Arthur; Licht, Jonathan D
- Abstract
The PLZF gene was identified by its fusion with the RARα locus in a therapy resistant form of acute promyelocytic leukemia (APL) associated with the t(11;17)(q23;q21) translocation. Here we describe PLZF as a negative regulator of cell cycle progression ultimately leading to growth suppression. PLZF can bind and repress the cyclin A2 promoter while expression of cyclin A2 reverts the growth suppressed phenotype of myeloid cells expressing PLZF. In contrast RARα-PLZF, a fusion protein generated in t(11;17)(q23;q21)-APL activates cyclin A2 transcription and allows expression of cyclin A in anchorage-deprived NIH3T3 cells. Therefore, cyclin A2 is a candidate target gene for PLZF and inhibition of cyclin A expression may contribute to the growth suppressive properties of PLZF. Deregulation of cyclin A2 by RARα-PLZF may represent an oncogenic mechanism of this chimeric protein and contribute to the aggressive clinical phenotype of t(11;17)(q23;q21)-associated APL.
- Subjects
LEUKEMIA; ACUTE myeloid leukemia; CELL cycle
- Publication
Oncogene, 1999, Vol 18, Issue 4, p925
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1202375