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
p21Waf1 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 p21Waf1 has alternative functions, and the view of its role in cellular processes has begun to change. At present, p21Waf1 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 p21Waf1 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 p21Waf1 is localized in the cytoplasm, it acts as an oncogene by regulating migration, apoptosis, and proliferation.
KEY WORDS: p21Waf1, oncogene, cell cycle, senescence, cytoplasmic localization, apoptosis