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

Weng Lang Yang, Yi Xin Zeng, Wafik S. El-Deiry, Kathryn Nason-Burchenal, Ethan Dmitrovsky, Khew Voon Chin

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)125-131
Number of pages7
JournalMolecular Cell Biology Research Communications
Volume1
Issue number2
DOIs
StatePublished - May 1999
Externally publishedYes

Keywords

  • Acute promyelocytic leukemia
  • p21
  • PML/RARα
  • Retinoic acid receptor
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology

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