title: TRIAD1 is negatively regulated by the MDM2 E3 ligase.
abstract: Two RING fingers and DRIL1 (TRIAD1) is a proapoptotic protein that promotes p53 activation in several cancer cell lines, including MCF7, U2OS and A549 cells. In this study, we demonstrated that TRIAD1 is a novel ubiquitination target for proteasome-dependent degradation by murine double minute 2 (MDM2). TRIAD1 was found to interact with and be ubiquitinated by MDM2. RNA interference against MDM2 increased endogenous TRIAD1 protein stability. The functional study results suggested that TRIAD1 degradation by MDM2 suppresses TRIAD1-mediated cell growth. These data suggested a novel negative regulatory mechanism of TRIAD1 via MDM2 E3 ligase ubiquitination.
authors.affiliation: Molecular-Targeted Drug Research Center, Konkuk University, Gwangjin-gu,                     Seoul 143-701, Republic of Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Bae
authors.forename: Jin Hyuk
authors.initials: JH
authors.lastname: Jung
authors.forename: In-Sook
authors.initials: IS
authors.lastname: An
authors.forename: Ok-Yeoun
authors.initials: OY
authors.lastname: Kim
authors.forename: Myoung Joo
authors.initials: MJ
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C506696:ARIH2 protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D044767:Ubiquitin-Protein Ligases