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

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

161 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
Externally published	Yes

Keywords

Acute promyelocytic leukemia
Cell cycle
Cyclin A
PLZF

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1038/sj.onc.1202375

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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

@article{fc159173ffe14a72a44de604c2e75966,

title = "Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A",

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.",

keywords = "Acute promyelocytic leukemia, Cell cycle, Cyclin A, PLZF",

author = "Yeyati, {Patricia L.} and Rita Shaknovich and Sima Boterashvili and Jia Li and Ball, {Helen J.} and Samuel Waxman and Kathryn Nason-Burchenal and Ethan Dmitrovsky and Arthur Zelent and Licht, {Jonathan D.}",

note = "Funding Information: We thank B Henglein, C Brechot and J Sobczak-Thepot for the cyclin A2 promoter constructs and fruitful discussions, JS Kang and RS Krauss for the cyclin-containing retroviral producer cell lines and M Serrano, N Hastie and J Caceres for careful reading of the manuscript. This work was supported by grants from the National Institutes of Health CA59936 (JDL, SW and AZ), CA62275 (ED) and the American Cancer Society grant DHP 116 (JDL). JDL is a Scholar of the Leukemia Society of America. PLY was supported by the Lauri Strauss Leukemia Fund. RS was supported by a Medical Scientist Training Grant GM0707280-17 from the NIH. KN-B was supported by National Research Service Award CA61646. HJB was supported by the Leukemia Research Foundation. This is publication #250 from the Brookdale Center for Developmental and Molecular Biology.",

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doi = "10.1038/sj.onc.1202375",

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T1 - Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A

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.

N1 - Funding Information: We thank B Henglein, C Brechot and J Sobczak-Thepot for the cyclin A2 promoter constructs and fruitful discussions, JS Kang and RS Krauss for the cyclin-containing retroviral producer cell lines and M Serrano, N Hastie and J Caceres for careful reading of the manuscript. This work was supported by grants from the National Institutes of Health CA59936 (JDL, SW and AZ), CA62275 (ED) and the American Cancer Society grant DHP 116 (JDL). JDL is a Scholar of the Leukemia Society of America. PLY was supported by the Lauri Strauss Leukemia Fund. RS was supported by a Medical Scientist Training Grant GM0707280-17 from the NIH. KN-B was supported by National Research Service Award CA61646. HJB was supported by the Leukemia Research Foundation. This is publication #250 from the Brookdale Center for Developmental and Molecular Biology.

PY - 1999/1/28

Y1 - 1999/1/28

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.

AB - 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.

KW - Acute promyelocytic leukemia

KW - Cell cycle

KW - Cyclin A

KW - PLZF

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DO - 10.1038/sj.onc.1202375

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JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 4

ER -

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

Abstract

Keywords

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