Transcriptional activation of the cyclin-dependent kinase inhibitor p21 by PML/RARα Journal Article


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
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