title: Direct interaction between p53 and Tid1 proteins affects p53 mitochondrial localization and apoptosis.
abstract: The p53 tumor suppressor induces apoptosis in response to genotoxic and environmental stresses. Separately from its functions as a transcription factor, it is also capable to be translocated to the mitochondria and plays a critical role in transcription-independent mitochondrial apoptosis. We previously demonstrated that Tid1 interacts with p53, resulting in mitochondrial translocation of the complex and induction of intrinsic apoptosis [1]; however, the mechanism how they interact has been unknown. In this study, far western analyses demonstrated that Tid1 directly interacted with p53. Using domain deletion mutant constructs, we determined that DnaJ domain of Tid1 was necessary for the interaction, while either N- or C-terminal domains of p53 were sufficient for the interaction. In breast cancer cells, depletion of Tid1 by short hairpin RNA (shRNA) led to absence of p53 accumulation at mitochondria and resistance to apoptosis under hypoxic or genotoxic stresses. Our studies imply that Tid1 could be important in the potential combination chemotherapies of p53-related cancers.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Diane L N
authors.initials: DLN
authors.lastname: Trinh
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Adam N
authors.initials: AN
authors.lastname: Elwi
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.|Southern Alberta Cancer Research Institute, Calgary, Alberta, T2N 4N1, Canada.|Clark H Smith Brain Tumour Centre, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C120664:DNAJA3 protein, human; D050956:HSP40 Heat-Shock Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53