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 Zelent; Jonathan D. Licht

doi:10.1038/sj.onc.1202375

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 Zelent, Jonathan D. Licht

Medicine

Research output: Contribution to journal › Article › peer-review

160 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 language	English (US)
Pages (from-to)	925-934
Number of pages	10
Journal	Oncogene
Volume	18
Issue number	4
DOIs	https://doi.org/10.1038/sj.onc.1202375
State	Published - Jan 28 1999

Keywords

Acute promyelocytic leukemia
Cell cycle
Cyclin A
PLZF

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A. / Yeyati, Patricia L.; Shaknovich, Rita; Boterashvili, Sima; Li, Jia; Ball, Helen J.; Waxman, Samuel; Nason-Burchenal, Kathryn; Dmitrovsky, Ethan; Zelent, Arthur; Licht, Jonathan D.

In: Oncogene, Vol. 18, No. 4, 28.01.1999, p. 925-934.

Research output: Contribution to journal › Article › peer-review

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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.",

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AU - Yeyati, Patricia L.

AU - Shaknovich, Rita

AU - Boterashvili, Sima

AU - Li, Jia

AU - Ball, Helen J.

AU - Waxman, Samuel

AU - Nason-Burchenal, Kathryn

AU - Dmitrovsky, Ethan

AU - Zelent, Arthur

AU - Licht, Jonathan D.

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N2 - 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.

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