Detail information of PPI "HPI051516"

IdentifierHPI051516
InteractionMdm2  <==>  p53
Role & StateRS:0000074,inhibitor; RS:0000002,activity; RS:0000080,suppressor; RS:0000068,activator;
Interaction TypeIT:0000128,phosphorylation; IT:0000092,degradation; IT:0000026,interact; IT:0000287,activate; IT:0000059,binding; IT:0000123,ubiquitination; IT:0000328,immunoprecipitate; IT:0000085,synthesis; IT:0000068,transcription; IT:0000077,regulate; IT:0000206,promote;
Biological ProcessBP:0006915,apoptosis; BP:0040007,growth;
Biological FunctionBF:0016874,ligase activity;
Subcelluar LocationSCL:0005818,aster;
Detection MethodDM:0000089,array;
Reference11799106_7, In contrast, Mdm2, an inhibitor of p53, was barely detectable in the immunoprecipitates.
Reference15625077_0, HMG-CoA reductase inhibitors, statins, induce phosphorylation of Mdm2 and attenuate the p53 response to DNA damage.
Reference17000718_1, Murine double minute 2 (Mdm2) negatively regulates p53 by mediating its ubiquitination and proteosomal degradation, and Mdm2 is recognized as a proto-oncogene.
Reference17000718_4, However, gene array analyses did not reveal changes in other p53-dependent genes, suggesting that induction of Mdm2 occurred in a p53-independent manner.
Reference17000718_7, Hepatic Mdm2 protein levels were increased, and immunohistochemical evaluation of rat liver demonstrated nuclear localization of Mdm2, suggesting an interaction with p53.
Reference17052188_7, Additionally, gankyrin, by binding to Mdm2, increases the ubiquitylation and degradation of p53 and prevents apoptosis.
Reference17107963_1, Mdm2 inactivates the tumor suppressor p53 and Akt has been shown to be a major activator of Mdm2 in many cell types.
Reference17107963_11, Ser-166 phosphorylation of Mdm2 has been shown to increase its ubiquitin ligase activity and increase p53 degradation, and our data indicated an attenuated p53 response to DNA damage in hepatocytes exhibiting high levels of pMdm2 Ser-166.
Reference21563203_9, CONCLUSION: Our findings indicate that KLF6 deficiency contributes significantly to the carcinogenic milieu in human and murine HCC and uncover a novel tumor suppressor activity of KLF6 in HCC by linking its transcriptional repression of Mdm2 to stabilizing p53.
Reference21747166_4, Hepatocyte-specific deletion in mice of the gene encoding Mdm2, a protein that promotes p53 degradation, led to hepatocyte synthesis of connective tissue growth factor (CTGF; the hepatic fibrogenic master switch), increased hepatocyte apoptosis, and spontaneous liver fibrosis; concurrent removal of p53 completely abolished this phenotype.