title: Nutrient/serum starvation derived TRIP-Br3 down-regulation accelerates apoptosis by destabilizing XIAP.
abstract: TRIP-Br3 and TRIP-Br1 have shown to have important biological functions. However, the function of TRIP-Br3 in tumorigenesis is not well characterized compared to oncogenic TRIP-Br1. Here, we investigated the function of TRIP-Br3 in tumorigenesis by comparing with that of TRIP-Br1. Under nutrient/serum starvation, TRIP-Br3 expression was down-regulated slightly in cancer cells and significantly in normal cells. Unexpectedly, TRIP-Br1 expression was greatly up-regulated in cancer cells but not in normal cells. Moreover, TRIP-Br3 activated autophagy while TRIP-Br1 inactivated it under serum starvation. In spite of different expression and roles of TRIP-Br3 and TRIP-Br1, both of them alleviate cell death by directly binding to and stabilizing XIAP, a potent apoptosis inhibitor, through blocking its ubiquitination. Taken together, we propose that TRIP-Br3 primarily activates the autophagy and suppresses apoptosis in nutrient sufficient condition. However, the prolonged extreme stressful condition of nutrient starvation causes a dramatic decrease of TRIP-Br3, which in turn induces apoptosis by destabilizing XIAP. Up-regulated TRIP-Br1 in cancer cells compensates this effect and delays apoptosis. This can be explained by the competitive alternative binding of TRIP-Br3 and TRIP-Br1 to the BIR2 domain of XIAP. In an extended study, our immunohistochemical analysis revealed a markedly lower level of TRIP-Br3 protein in human carcinoma tissues compared to normal epithelial tissues, implying the role of TRIP-Br3 as a tumor suppressor rather than onco-protein.
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Chengping
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Samil
authors.initials: S
authors.lastname: Jung
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Soonduck
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, Soonchunhyang University, Chonan, 330-090, South Korea.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Keun-Il
authors.initials: KI
authors.lastname: Kim
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Chung-Il
authors.initials: CI
authors.lastname: Cheon
authors.affiliation: Department of Pathology, College of Medicine, Soonchunhyang University, Chonan, 330-090, South Korea.
authors.forename: Changjin
authors.initials: C
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Young-Sook
authors.initials: YS
authors.lastname: Kang
authors.affiliation: Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
mesh_terms: D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D014162:Transfection; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000032:analysis / Q000378:metabolism*
chemical_list: C515965:CDCA4 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein
keywords: TRIP-Br1; TRIP-Br3; XIAP; apoptosis; nutrient/serum starvation