Its expression was negatively correlated to that of p21(WAF1) protein; p53RFP is likely to play a role in the regulation of this protein, probably through interaction with, and ubiquitination of, p21(WAF1).
Using a p21 expression vector encoding an alanine substitution at Thr145, the half-life of the protein was nearly identical in the absence or in the presence of transfected ZIP kinase (Figure 7(C) versus (D)).
These results implicate galectin-8 as a modulator of cellular growth through up-regulation of p21. This process involves activation of JNK, which enhances the synthesis of p21, combined with the activation of PKB, which inhibits p21 degradation
As shown in Fig. 3C, phosphorylation on Thr145 site can increase the steady-state level of transfected p21 as does Thr145Asp/Ser146Asp (DD). On the other hand, Ser146Asp (S/D) mutants showed no stabilizing effect compared with WT p21.
GSK-3 triggers p21(Cip1) degradation. In contrast, stimulation of AKT increases p21(Cip1) via inhibitory phosphorylation of GSK-3.
p53RFP is involved in ubiquitination and degradation of p21, a p53 downstream protein promoting growth arrest and antagonizing apoptosis,
UV and IR both target p21 protein for degradation immediately after DNA damage
The described role of Skp2 in inducing the ubiquitinylation and degradation of the tumor suppressor p27,and more recently of p21, p57 and p130, indicates that Skp2 may be the product of a proto-oncogene an inverse relationship between Skp2 and p27 protein levels was found in human lymphomas, breast carcinomas epithelial dysplasias, colorectal carcinomas, oral squamous cell carcinomas small cell lung cancers gastric carcinomas and prostate cancers
ZIP kinase phosphorylates p21(WAF1) at Thr145. Transfected ZIPK can promote the phosphorylation of p21(WAF1) at Thr145 in vivo and can increase the half-life of p21(WAF1)
SKP2 targets negative regulators of the cell cycle such as p27, p21 and p57 for degradation, and thereby promotes cell cycle progression during S and G2 phases. SKP2 is upregulated in many human cancers.
Skp2 and its cofactor Cks1 are the substrate-targeting subunits of the SCF(Skp2-Cks1) (Skp1/Cul1/F-box protein) ubiquitin ligase complex that regulates entry into S phase by inducing the degradation of the cyclin-dependent kinase inhibitors p21 and p27
Cdc42/Rac1 signaling pathway activates proteasomal degradation of p21(CIP1).
Therefore, MDM2 mutants without amino acids 251-260 (but not without other amino acids of the acidic domain of MDM2) lose the ability to promote the C8 binding and subsequent degradation of p21Waf1 (Fig. 4E).
These data show that GSK-3beta is activated by UV irradiation through the ATR signaling pathway and phosphorylates p21 at ser-114 for its degradation by the proteasome. # p21 = CDKN1A
p38 alpha and JNK1 phosphorylated p21 in vivo, and both p38 alpha and JNK1 phosphorylated p21 at Ser(130) in vitro.Peptide mapping demonstrated that both TGF-beta 1 and p38 alpha induced phosphorylation of p21 at Ser(130) in vivo, and mutation of Ser(130) to alanine rendered p21 less stable than wild-type p21.
TNF-alpha-induced apoptosis in LNCaP cells was accompanied by caspase-dependent proteolysis of p21/WAF1 and Rb, which was significantly attenuated in LN-56.
Using the proteasome-specific inhibitors, MG132 and lactacystin, we show that the p53, the cdk inhibitors p21 and p27, and cyclin A are degraded by the ubiquitin-proteasome pathway in human osteosarcoma cells.
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