Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A.
Oncogene
; 18(4): 925-34, 1999 Jan 28.
Article
en En
| MEDLINE
| ID: mdl-10023668
ABSTRACT
The PLZF gene was identified by its fusion with the RARalpha 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 RARalpha-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 RARalpha-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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Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Leucemia Promielocítica Aguda
/
Proteínas de Fusión Oncogénica
/
Ciclo Celular
/
Ciclina A
/
Proteínas de Unión al ADN
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
1999
Tipo del documento:
Article
País de afiliación:
Estados Unidos