Authors: | Yang, W. L.; Zeng, Y. X.; El-Deiry, W. S.; Nason-Burchenal, K.; Dmitrovsky, E.; Chin, K. V. |
Article Title: | Transcriptional activation of the cyclin-dependent kinase inhibitor p21 by PML/RARα |
Abstract: | Acute promyelocytic leukemia (APL) is a result of clonal expansion of hematopoietic precursors blocked, at the promyelocytic stage and is associated with a t(15;17) chromosomal translocation and the expression of the PML/RARa fusion protein. Treatment of APL cells with retinoic acid (RA) leads to complete remission by inducing growth arrest and differentiation of these cells into granulocytes. The cyclin-dependent kinase inhibitor p21WAF1/CIP1 may be involved in terminal differentiation associated growth arrest. We showed in this study that PML/RARα increased the transcription of p21WAF1/CIP1 gene and the activation was further induced by RA treatment. Deletion analysis revealed a region upstream of the p21WAF1/CIP1 promoter that is required for transactivation by PML/RARα. Transient transfection of PML/RARα in cells increased the endogenous p21WAF1/CIP1 protein levels. These results suggest that the induction of APL cells differentiation by RA may be a result of the activation of p21WAF1/CIP1 by PML/RARα. © 1999 Academic Press. |
Keywords: | immunohistochemistry; promoter region; gene deletion; genetics; sequence deletion; metabolism; nuclear protein; neoplasm proteins; protein binding; transcription factor; tumor cells, cultured; hela cell; hela cells; transfection; physiology; transcription factors; nuclear proteins; drug antagonism; genetic transfection; cell culture; tumor suppressor proteins; tumor protein; transactivation; transcription; cyclin dependent kinase inhibitor 1a; cyclin-dependent kinase inhibitor p21; cycline; tumor suppressor protein; cyclin-dependent kinases; cyclins; cyclin dependent kinase; cell extracts; cdkn1a protein, human; acute promyelocytic leukemia; pml/rarα; retinoic acid receptor alpha; retinoic acid receptor; cell extract; receptors, retinoic acid; promoter regions (genetics); trans-activation (genetics); hl-60 cells; cell strain hl 60; pml protein, human; humans; human; article; p21waf1/cip1 |
Journal Title: | Molecular Cell Biology Research Communications |
Volume: | 1 |
Issue: | 2 |
ISSN: | 1522-4724 |
Publisher: | Academic Press, Elsevier Inc |
Date Published: | 1999-05-01 |
Start Page: | 125 |
End Page: | 131 |
Language: | English |
PUBMED: | 10356361 |
PROVIDER: | scopus |
DOI: | 10.1006/mcbr.1999.0121 |
DOI/URL: | |
Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |