Leukemia translocation protein PLZF inhibits cell growth and expression of cyclin A Journal Article
| Authors: | Yeyati, P. L.; Shaknovich, R.; Boterashvili, S.; Li, J.; Ball, H. J.; Waxman, S.; Nason-Burchenal, K.; Dmitrovsky, E.; Zelent, A.; Licht, J. D. |
| Article 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: | gene translocation; human cell; promoter region; dna-binding proteins; phenotype; animals; mice; cell cycle; cell cycle s phase; gene expression; cell growth; neoplasm proteins; gene locus; genetic vectors; transcription factors; leukemia, promyelocytic, acute; acute myeloblastic leukemia; oncogene proteins, fusion; translocation, genetic; bone marrow cell; cyclin-dependent kinases; cyclin a; chromosomes, human, pair 11; s phase; cell strain 3t3; 3t3 cells; chromosomes, human, pair 17; acute promyelocytic leukemia; zinc fingers; plzf; interphase; humans; human; priority journal; article |
| Journal Title: | Oncogene |
| Volume: | 18 |
| Issue: | 4 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1999-01-28 |
| Start Page: | 925 |
| End Page: | 934 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1202375 |
| PUBMED: | 10023668 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
