title: p21Cip1/Waf1 protein and its function based on a subcellular localization [corrected].
abstract: Protein p21(Cip1/Waf1) is a cyclin-dependent kinase inhibitor, which is important in the response of cells to genotoxic stress and a major transcriptional target of p53 protein. Based on the localization, p21(Cip1/Waf1) protein executes various functions in the cell. In the nucleus p21(Cip1/Waf1) binds to and inhibits the activity of cyclin dependent kinases Cdk1 and Cdk2 and blocks the transition from G1 phase into S phase or from G2 phase into mitosis after DNA damage. This enables the repair of damaged DNA. p21(Cip1/Waf1) was also found as an important protein for the induction of replication senescence as well as stress-induced premature senescence. In the cytoplasm, p21(Cip1/Waf1) protein has an anti-apoptotic effect. It is able to bind to and inhibit caspase 3, as well as the apoptotic kinases ASK1 and JNK. The function of p21(Cip1/Waf1) in response to a DNA damage probably depends on the extent of the damage. In the case of low-level DNA damage, the expression of p21(Cip1/Waf1) is increased, it induces cell cycle arrest, and performs also anti-apoptotic activities. However, after extensive DNA damage the amount of p21(Cip1/Waf1) protein is decreased and the cell undergoes apoptosis. Dual function of p21(Cip1/Waf1) was also observed in cancerogenesis. On the one hand, p21(Cip1/Waf1) acts as a tumor suppressor; on the other hand it prevents apoptosis and acts as an oncogene. Better understanding of the role of p21(Cip1/Waf1) in various conditions would help to develop better cancer-treatment strategies.
authors.affiliation: Department of Medical Biochemistry, Charles University in Prague, Medical Faculty in Hradec Králové, Šimkova 870, 500 38 Hradec Králové 1, Czech Republic. cmielovaj@lfhk.cuni.cz
authors.forename: Jana
authors.initials: J
authors.lastname: Cmielová
authors.forename: M
authors.initials: M
authors.lastname: Rezáčová
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D011499:Protein Processing, Post-Translational; D013347:Subcellular Fractions / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21