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

Mol Cell Biol Res Commun. 1999 May;1(2):125-31. doi: 10.1006/mcbr.1999.0121.


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/RARalpha 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/RARalpha 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/RARalpha. Transient transfection of PML/RARalpha 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/RARalpha.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Extracts
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclins / genetics
  • Cyclins / metabolism*
  • HL-60 Cells
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / physiology*
  • Nuclear Proteins*
  • Promoter Regions, Genetic
  • Promyelocytic Leukemia Protein
  • Protein Binding
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Retinoic Acid / physiology*
  • Retinoic Acid Receptor alpha
  • Sequence Deletion
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins


  • CDKN1A protein, human
  • Cell Extracts
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • RARA protein, human
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Cyclin-Dependent Kinases