Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A

Patricia L. Yeyati, Rita Shaknovich, Sima Boterashvili, Jia Li, Helen J. Ball, Samuel Waxman, Kathryn Nason-Burchenal, Ethan Dmitrovsky, Arthur Z Zelent, Jonathan D. Licht

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159 Scopus citations

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 phenotygpe 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.

Original languageEnglish (US)
Pages (from-to)925-934
Number of pages10
JournalOncogene
Volume18
Issue number4
DOIs
StatePublished - Jan 28 1999
Externally publishedYes

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Keywords

  • Acute promyelocytic leukemia
  • Cell cycle
  • Cyclin A
  • PLZF

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Yeyati, P. L., Shaknovich, R., Boterashvili, S., Li, J., Ball, H. J., Waxman, S., Nason-Burchenal, K., Dmitrovsky, E., Zelent, A. Z., & Licht, J. D. (1999). Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A. Oncogene, 18(4), 925-934. https://doi.org/10.1038/sj.onc.1202375