p21Cip1/WAF1 is important for differentiation and survival of U937 cells

Leukemia. 1998 Dec;12(12):1944-50. doi: 10.1038/sj.leu.2401228.


Vitamin D3 (VD3) induces monocytic differentiation of U937 cells. Induction of p21Cip1/WAF1 (p21) and subsequent G0/G1 cell-cycle arrest are required in this process. Using a system of inducible expression of ectopic p21, we demonstrated the important role of p21 in the induction of monocytic differentiation in U937 cells. Prior induction of antisense-p21 expression significantly suppressed p21 expression, and resulted in inhibition of VD3-induced U937 differentiation. Moreover, induction of expression of antisense-p21 in VD3-differentiated U937 cells resulted in apoptosis of the cells. This was associated with activation of Cdc2 and caspase-3 like protease. Our results suggest that p21 is required for the initiation of the early steps of differentiation as well as survival of differentiated cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • CD11 Antigens / metabolism
  • Caspases / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation / physiology*
  • Cell Survival
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Cyclins / metabolism
  • Cyclins / physiology*
  • Humans
  • Macrophages / cytology
  • Monocytes / cytology
  • Transfection
  • U937 Cells
  • Zinc Sulfate / pharmacology


  • CD11 Antigens
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Zinc Sulfate
  • Caspases