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 language | English (US) |
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Pages (from-to) | 125-131 |
Number of pages | 7 |
Journal | Molecular Cell Biology Research Communications |
Volume | 1 |
Issue number | 2 |
DOIs | |
State | Published - May 1999 |
Externally published | Yes |
Keywords
- Acute promyelocytic leukemia
- PML/RARα
- Retinoic acid receptor
- Transcription
- p21
ASJC Scopus subject areas
- Molecular Biology