IndraLab

"The latter process relies on interactions between the p53 ubiquitin ligase MDM2 and ribosomal proteins (RPs) [ xref ]."

"The interaction between p53 and E3 ligases such as MDM2, all transcription targets of p53, leads to the ubiquitination and rapid degradation of p53."

"In the absence of cellular stress, p53 is bound by its negative regulator, Mdm2, an E3 ubiquitin ligase that promotes its degradation."

"This phosphorylation interrupts the interaction between MDM2, a ubiquitin ligase, and p53, thereby preventing proteasomal degradation of p53 [ xref ]."

"Nuclear FAK can influence cell survival, through its formation of a p53 and E3 ligase mdm-2 degradation complex."

"An MDM2 mutant lacking E3 ligase activity also binds wild-type p53 efficiently and inhibits p53 activation [ xref ]."

"However, recent research has shown that Mdm2-p53 binding alone in the absence of Mdm2 E3 ubiquitin ligase activity is insufficient to suppress p53 activity [ xref ]."

"The inherent adaptability of IDPs is also demonstrated by the somewhat different molecular logic of E3 MDM2 (murine double minute 2) binding to its premium substrate, p53."

"For detailed information on the interactions of MDM2 and other E3 ligases with the p53 family members, see the reviews [ xref , xref , xref , xref , xref , xref , xref , xref , xref ]."

"A similar strategy has been successfully applied to the selective cancer cell blockade of interactions between mdm2 ubiquitin ligase and p53 using nutlins [ xref ]."

"Epstein Barr virus (EBV) nuclear antigen 3C (EBNA3C) forms a trimeric complex with p53 and Mdm2, which enhances the ubiquitin ligase activity of Mdm2 for p53."

"Some of these modifications are known to influence the interaction between p53 and the E3 ubiquitin ligase, MDM2, which is a major mechanism for controlling p53 through inducing proteasomal degradation."

"This modification impairs the interaction between p53 and MDM2, the main negative regulatory E3 ubiquitin ligase of p53, to relieve both ubiquitin-dependent and ubiquitin-independent repression mediated by MDM2 from p53 xref , xref ."

"We note that the p53–COP1 interaction is characterized by a higher affinity and by a longer lifetime with respect to the complex formed by p53 and its major ubiquitin ligase, MDM2, strengthening the importance of COP1 in p53 downregulation."

"DHCR24 overexpression in these cells paralleled the increased interaction between p53 and MDM2 (also known as HDM2), a p53-specific E3 ubiquitin ligase, in the cytoplasm."

"No inhibitors of RABL6A currently exist, but various types of MDM2 inhibitors have been developed that either inhibit the MDM2-p53 interaction, its E3 ligase activity, or dampen its expression [ xref – xref ]."

"Furthermore, another MDM2 inhibitor, Nutlin3, known to block the MDM2-p53 interaction without inhibiting the overall ubiquitin ligase activity of MDM2 xref , xref did not promote the activation of NFATc2 or the induction of cytokines in wild-type naïve CD4 + T cells, although Nutlin-3 did enhance the induction of the p53 target gene p21 ( xref )."

"The ubiquitylation of GR requires p53, the interaction of p53 with Hdm2, and E3 ligase activity of Hdm2."

"For instance, Numb is an important p53 regulator by forming a tripartite complex with tumor suppressor p53 and its E3 ligase, Mdm2, thus inhibiting the degradation of p53 and promoting its tumor suppressive functions. xref Many other functions of Numb, such as muscle stem cell proliferation and regeneration, xref endocytosis and ubiquitination, have also been reported. xref Recently, it was shown that post-translational modifications, including phosphorylation and methylation, can affect Numb functions like asymmetric distribution as well as tumor suppressive roles based on its regulation on p53. xref – xref p53, a well-studied transcription factor, is crucial for mediating cell cycle arrest and apoptosis in response to DNA damage. xref Further, it has been documented that disruption of the p53 pathway has always been associated with therapeutic resistance and poor clinical outcomes. xref Of note, cancer cells without Numb are less sensitive to chemotherapeutic drugs than cells expressing a functional Numb. xref Thus, understanding how Numb is regulated will provide us novel opportunities for improving the efficacy of existing chemotherapy."

"To this regard, before p53 induction, a disruption between the complex formed by p53 and MDM2, a p53-specific E3 ubiquitin ligase, is needed for its biological response [19] ."

"Mdm2 effects on p53 are attributed to the abundance of Mdm2 expression, the levels of Mdm2-p53 association, and modulation of Mdm2 ubiquitin ligase activity."

"As shown in table xref , there are three main categories of MDM2 inhibitors: inhibitors of MDM2-p53 interaction by targeting to MDM2, inhibitor of MDM2-p53 interaction by targeting to p53, and inhibitors of MDM2 E3 ubiquitin ligase."

"The best studied function of p14ARF is its interaction with and inhibition of two ubiquitin ligases, MDM2 and ARF-BP1/Mule, which target p53 for degradation [ xref , xref ] thus potentiating p53 activity [ xref ]."

"Phosphorylation of p53 at the N-terminus has previously been shown to disrupt the interaction between p53 and its ubiquitin ligase, MDM2, and therefore stabilizing p53."

"The interaction between E3 ubiquitin ligase Mdm2 and p53 proteins usually drives p53 for degradation by the proteasome."