Protein and its function based on a subcellular localization

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.

Silencing of ATPase Inhibitory Factor 1 Inhibits Cell Growth via Cell Cycle Arrest in Bladder Cancer

“…The p21 protein is the first identified cdk inhibitor and plays a critical role in cell cycle progression [22]. It effectively inhibits cdk2, cdk4 and cdk6 by blocking kinase activity or interfering with activating phosphorylation, which have a direct function in G 1 /S transition [23].…”

Oncogenic role of p21 in hepatocarcinogenesis suggests a new treatment strategy

“…The dual functions of p21, apoptotic or anti-apoptotic, depend on its subcellular localization [9,46] . Nuclear p21 is anti-proliferative and cytoplasmic p21, which is antiapoptotic, may be associated with oncogenic function.…”

C/EBPα regulates CRL4Cdt2-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint

“…34 Therefore, we prepared cytosolic and nuclear protein extracts from UVB-treated control and C/EBPa knockdown keratinocytes to determine whether C/EBPa deficiency preferentially affects nuclear p21 protein levels. The knockdown of C/EBPa had only a modest effect on UVB-induced cytosolic p21 levels, however, nuclear p21 protein levels failed to increase after UVB exposure in C/EBPa-deficient keratinocytes ( Fig.…”