REVIEW: Cyclin-Dependent Kinase Inhibitor p21^Waf1: Contemporary View on Its Role in Senescence and Oncogenesis

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V. S. Romanov^1,2*, V. A. Pospelov^1,3, and T. V. Pospelova^1,3

¹Institute of Cytology, Russian Academy of Sciences, Tikhoretsky pr. 4, 194064 St. Petersburg, Russia; fax: (812) 297-3541; E-mail: vsromanov@hotmail.com

²Leibniz Institute for Age Research – Fritz Lipmann Institute, Beutenbergstraße 11, D-07745 Jena, Germany

³St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia

^* To whom correspondence should be addressed.

Received February 24, 2012; Revision received March 15, 2012

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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.

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KEY WORDS: p21^Waf1, oncogene, cell cycle, senescence, cytoplasmic localization, apoptosis

DOI: 10.1134/S000629791206003X

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