IndraLab
Statements
reach
"P53, as a tumour-suppressor, exerts an essential role in signalling associated with the control of cell survival and aberrant p53 signalling results in unchecked cell growth and the initiation of cancer.USP7 interacts with a range of protein targets in the p53 pathway (p53, MDMX, MDM2)39 and MDM2 plays a key role in p53 stabilization by increasing the ubiquitination process.39 USP7 deubiquitinates MDM2 and its functional regulator MdmX and stabilizes p53.39 USP7 apparently has 2 independent p53 regulatory functions, stabilizing p53 through deubiquitylation and regulating the sequence-specific DNA binding of p53.40 Within the USP7, MDM2 and p53 complex, p53 and the MDM2 have been shown to bind USP7 through the TRAF domain.39 Under normal conditions, USP7 prefers MDM2 as a substrate rather than p53 and MDM2 has a higher binding affinity for USP7 compared to p53.41 Reduction of USP7 expression levels leads to p53 stabilisation, and destabilization of MDM2."
sparser
"USP7 interacts with a range of protein targets in the p53 pathway (p53, MDMX, MDM2) xref and MDM2 plays a key role in p53 stabilization by increasing the ubiquitination process. xref USP7 deubiquitinates MDM2 and its functional regulator MdmX and stabilizes p53. xref USP7 apparently has 2 independent p53 regulatory functions, stabilizing p53 through deubiquitylation and regulating the sequence-specific DNA binding of p53. xref Within the USP7, MDM2 and p53 complex, p53 and the MDM2 have been shown to bind USP7 through the TRAF domain. xref Under normal conditions, USP7 prefers MDM2 as a substrate rather than p53 and MDM2 has a higher binding affinity for USP7 compared to p53. xref Reduction of USP7 expression levels leads to p53 stabilisation, and destabilization of MDM2."
sparser
"For example, by interacting with ubiquitin-specific protease USP7 (as discussed below), it has been suggested that EBNA1 could interfere with p53’s or MDM2’s own binding to USP7, leading in particular to lower levels of the p53 transcriptional activator, thereby promoting cell survival in response to cellular stress [ xref , xref , xref , xref , xref ]."
sparser
"Moreover, p53 was found to be upregulated in MDM2 −/− p53 −/− double-deficient MEFs after co-transfection of both p53 and ABRO1, indicating that ABRO1-dependent p53 stabilization is made possible by enhanced p53-USP7 interaction without effects on p53-MDM2 interaction and MDM2 stability."
sparser
"In a similar experiment, alanine substitutions of NTD residues known to be important for interactions of USP7 substrates such as p53 and MDM2 ( xref , xref ) led to loss of (W 149 A and DWGFS 152 A 5 ) or greatly diminished (R 88 A) interaction of the residue 1 to 220 USP7 fragment with vIRF-2 (data not shown), indicating canonical interaction of the vIRF-2 PSTS motif with the USP7 TRAF-like domain despite the additional requirements for vIRF-2 and its binding region (residues 241 to 260) to interact with USP7."