p53 stabilization can be uncoupled from its role in transcriptional activation by loss of PTTG1/securin.
HCT116 cells devoid of PTTG1/securin (sec(-/-) HCT116) show a stabilized yet transcriptionally latent form of p53 protein in the absence of DNA damage. Ser15, Ser20 phosphorylation and other post-transcriptional modifications of p53 resolved by 2D gel electrophoresis are comparable to that observed in sec(+/+) HCT116 cells. The difference in degradation was also shown to be independent of the ubiquitin system but reliant on calpains. However, the p53-mediated checkpoint response is active only after genotoxic stress in sec(-/-) HCT116 cells. These findings point to the calpain pathway as a key player to maintain steady state levels of p53 in resting cells without affecting its activity.
Bernal
Juan A
JA
Centro Andaluz de Biología Molecular y Medicina Regenerativa (C.S.I.C.) Avda. Americo Vespucio s/n 41092 Seville, Spain.
Hernández
Agustín
A
D000595:Amino Acid Sequence; D002154:Calpain / Q000502:physiology; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D006801:Humans; D009363:Neoplasm Proteins / Q000172:deficiency / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D064249:Securin; D012694:Serine / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*; D025801:Ubiquitin / Q000502:physiology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; D064249:Securin; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C578002:pituitary tumor-transforming protein 1, human; D012694:Serine; D002154:Calpain