Apr 16, 2004 · Here we provide evidence supporting functional interaction between MDM2 and p21 in vitro and in vivo. The inhibition of MDM2 with anti-MDM2 antisense oligonucleotide or Short Interference RNA targeting MDM2 significantly elevated p21 protein levels in PC3 cells (p53 null).

MDM2 shortened the half-life of both exogenous and endogenous p21 waf1/cip1 by 50% and led to the degradation of its lysine-free mutant. Consequently, MDM2 suppressed p21 waf1/cip1 -induced cell growth arrest of human p53–/– and p53–/–/Rb–/– cells.

Dec 1, 2003 · MDM2 shortened the half‐life of both exogenous and endogenous p21 waf1/cip1 by 50% and led to the degradation of its lysine‐free mutant. Consequently, MDM2 suppressed p21 waf1/cip1 ‐induced cell growth arrest of human p53−/− and p53−/−/Rb−/− cells.

This version of p21 was capable of interacting with cyclin-dependent kinase 2 (Cdk2) but failed to inhibit its activity. Taken together, these results argue that Mdm2 is needed for full inhibition of Cdk2 activity by p21, thereby positively contributing to p53-dependent cell cycle arrest.

Following cellular stress, p53 induces the expression of the cyclin-dependent kinase (cdk) inhibitor p21, among other target genes. p21 is a key mediator of arrest at the G 1 phase of the cell cycle and contributes to the G 2 arrest (6, 47).

Mar 3, 2009 · We uncovered that MDM2 released from p53 by RITA promotes degradation of p21 and the p53 cofactor hnRNP K, required for p21 transcription. Functional studies revealed MDM2-dependent inhibition of p21 as a key switch regulating cell fate decisions upon p53 reactivation.

MDM2 binds to p21 and promotes p21 proteasomal degradation . We assessed MDM2 involvement in the fluoride-mediated decrease of p21 protein levels observed at 24 h. The co-IP result shows that NaF (5 mM) treatment for 6 h increased MDM2-p21 binding which was suppressed by Nutlin-3a (Figure 7a).

May 10, 2019 · These results suggest that MDM2-mediated p21 proteasomal degradation with subsequent phospho-p21 attenuation contributes to fluoride-induced apoptosis. Inhibition of MDM2-mediated p21 degradation may be a potential …

Jun 11, 2010 · MDM2 and p21 Waf1 co-localize in the nucleus, and mutations to the NLS, NES, and AD of MDM2 prevent its degradation of p21 Waf1. HCT116 (p53 −/−) cells were grown on coverslips for 24 h and transfected with either wild-type …

Apr 16, 2004 · MDM2 facilitates p21 degradation independent of ubiquitination and the E3 ligase function of MDM2. Instead, MDM2 promotes p21 degradation by facilitating binding of p21 with the proteasomal C8 subunit.