Nov 17, 2024 · TRAF6 triggers K63-linked ubiquitination of p53 at K24 in the cytoplasm, which reduces the interaction between p53 and MCL-1/BAK, thus keeping p53 away from mitochondria and preventing p53 mediated activation of BAK.

Oct 6, 2022 · Deubiquitinase CYLD promotes DNA damage-induced p53 activation by removing K48-ubiquitin chains from p53 and cleaving K63-ubiquitin, which regulates p53 responses to genotoxic stress in cancer...

Nov 17, 2016 · Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction between p53 and MCL-1/BAK.

Feb 14, 2022 · P53 is predominantly ubiquitinated in a K48-linked manner for degradation, while K63-linked ubiquitination of P53 enhances its stability and inhibits K48-linked ubiquitination.

Nov 22, 2016 · The amount of K63-linked ubiquitylated p53 decreased upon genotoxic stress in conjunction with an increase in the abundance of p53 at mitochondria. Overexpression of various E3 ubiquitin ligases identified TRAF6 as responsible for this modification.

TRAF6 triggers K63-linked ubiquitination of p53 at K24 in the cytoplasm, which reduces the interaction between p53 and MCL-1/BAK, thus keeping p53 away from mitochondria and preventing p53-medi-ated activation of BAK.

Jun 15, 2012 · LMP1 promoted p53 stability and accumulation by suppressing K48-linked ubiquitination of p53 mediated by E3 ligase MDM2, which is associated with its phosphorylation at Ser20, while increasing the levels of total cellular ubiquitinated p53.

For example, efforts have been invested on targeting HDM2, the E3 ligase for tumor suppressor p53, aiming to elevate the protein level of p53. Nutlin 3/R7112, an inhibitor that disrupts the interaction between HDM2 and its substrate p53, has entered clinical trials (Cohen and Tcherpakov, 2010 ).

Jan 15, 2015 · Mdm2 is a critical negative regulator of the tumor suppressor protein p53. Mdm2 is an E3 ligase whose overexpression leads to functional inactivation of p53. Mdm2 protein stability is regulated by several mechanisms including RING (Really Interesting New Gene) domain-mediated autoubiquitination.

Nov 25, 2024 · We demonstrate how USP53 mutations abrogate catalytic activity, implicating loss of DUB activity in USP53 -mediated pathology. Depletion of USP53 increases K63-linked ubiquitination of...