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 | |
| State | Published - Jan 28 1999 |
| Externally published | Yes |
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Keywords
- Acute promyelocytic leukemia
- Cell cycle
- Cyclin A
- PLZF
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
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 Z; Licht, Jonathan D.
In: Oncogene, Vol. 18, No. 4, 28.01.1999, p. 925-934.Research output: Contribution to journal › Article
}
TY - JOUR
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 Z
AU - Licht, Jonathan D.
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
UR - http://www.scopus.com/inward/record.url?scp=0001281430&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0001281430&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1202375
DO - 10.1038/sj.onc.1202375
M3 - Article
C2 - 10023668
AN - SCOPUS:0001281430
VL - 18
SP - 925
EP - 934
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 4
ER -