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Protein and its function based on a subcellular localization
Author(s) -
Ćmielová Jana,
Řezáčová M.
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23296
Subject(s) - dna damage , microbiology and biotechnology , cyclin dependent kinase 1 , cell cycle , cyclin dependent kinase 2 , kinase , biology , cyclin a , dna repair , mitosis , apoptosis , senescence , cell cycle checkpoint , protein kinase a , cyclin dependent kinase , dna , biochemistry
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. J. Cell. Biochem. 112: 3502–3506, 2011. © 2011 Wiley Periodicals, Inc.