title: Inhibition of tumor suppressor protein p53-dependent transcription by a tetramerization domain peptide via hetero-oligomerization.
abstract: Tumor suppressor protein p53 induces cell cycle arrest, apoptosis, and senescence in response to cellular stresses. The p53 tetramer formation is essential for its functions. Despite of these crucial functions of p53 for integrity of genome, activation of the p53 signal pathway causes low induced pluripotent stem (iPS) cell generation efficiency. In this study, we report transient inhibition of p53-dependent transcription using a p53 tetramerization domain peptide that contains cell penetrating and nuclear localization signals. The peptide was efficiently introduced into cells and inhibited p21 expression via hetero-tetramerization with endogenous p53 protein. This method can be applied towards safe and efficient iPS cell generation.
authors.affiliation: Department of Chemistry, Faculty of Science, Hokkaido University, Kita-ku, Sapporo, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Wada
authors.forename: Rui
authors.initials: R
authors.lastname: Kamada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Imagawa
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Chuman
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Sakaguchi
mesh_terms: D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D010455:Peptides; D016159:Tumor Suppressor Protein p53