title: TRIAD1 inhibits MDM2-mediated p53 ubiquitination and degradation.
abstract: Murine double minute (MDM2) is an E3 ligase that promotes ubiquitination and degradation of tumor suppressor protein 53 (p53). MDM2-mediated regulation of p53 has been investigated as a classical tumorigenesis pathway. Here, we describe TRIAD1 as a novel modulator of the p53-MDM2 axis that induces p53 activation by inhibiting its regulation by MDM2. Ablation of TRIAD1 attenuates p53 levels activity upon DNA damage, whereas ectopic expression of TRIAD1 promotes p53 stability by inhibiting MDM2-mediated ubiquitination/degradation. Moreover, TRIAD1 binds to the C-terminus of p53 to promote its dissociation from MDM2. These results implicate TRIAD1 as a novel regulatory factor of p53-MDM2.
authors: Molecular-Targeted Drug Research Centre, Konkuk University, Seoul, Republic of Korea.
authors: Seunghee
authors: S
authors: Bae
authors: Jin Hyuk
authors: JH
authors: Jung
authors: Karam
authors: K
authors: Kim
authors: In-Sook
authors: IS
authors: An
authors: Soo-Yeon
authors: SY
authors: Kim
authors: Jae Ho
authors: JH
authors: Lee
authors: In-Chul
authors: IC
authors: Park
authors: Young-Woo
authors: YW
authors: Jin
authors: Su-Jae
authors: SJ
authors: Lee
authors: Sungkwan
authors: S
authors: An
mesh_terms: D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D004249:DNA Damage; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D054730:Protein Interaction Domains and Motifs; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C506696:ARIH2 protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D044767:Ubiquitin-Protein Ligases