Cyclin-dependent kinase inhibitor p21(Waf1): contemporary view on its role in senescence and oncogenesis

Biochemistry (Mosc). 2012 Jun;77(6):575-84. doi: 10.1134/S000629791206003X.


p21(Waf1) was identified as a protein suppressing cyclin E/A-CDK2 activity and was originally considered as a negative regulator of the cell cycle and a tumor suppressor. It is now considered that p21(Waf1) has alternative functions, and the view of its role in cellular processes has begun to change. At present, p21(Waf1) is known to be involved in regulation of fundamental cellular programs: cell proliferation, differentiation, migration, senescence, and apoptosis. In fact, it not only exhibits antioncogenic, but also oncogenic properties. This review provides a contemporary understanding of the functions of p21(Waf1) depending on its intracellular localization. On one hand, when in the nucleus, it serves as a negative cell cycle regulator and tumor suppressor, in particular by participating in the launch of a senescence program. On the other hand, when p21(Waf1) is localized in the cytoplasm, it acts as an oncogene by regulating migration, apoptosis, and proliferation.

Publication types

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

MeSH terms

  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Apoptosis / physiology
  • Cell Cycle / physiology
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Physiological Phenomena / physiology*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cellular Senescence / physiology
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Cytoplasm / genetics
  • Cytoplasm / metabolism
  • Humans


  • Cyclin E
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase 2