TRIP-Br1 oncoprotein inhibits autophagy, apoptosis, and necroptosis under nutrient/serum-deprived condition
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Samil Jung1,*, Chengping Li1,*, Jingjing Duan1, Soonduck Lee1, Kyeri Kim1, Yeonji Park1, Young Yang1, Keun-Il Kim1, Jong-Seok Lim1, Chung-Il Cheon1, Young-Sook Kang2, Myeong-Sok Lee1
1Department of Life Systems, Sookmyung Women’s University, Seoul, 140-742, South Korea
2College of Pharmacy, Sookmyung Women’s University, Seoul, 140-742, South Korea
*These authors have contributed equally to this work
Myeong-Sok Lee, e-mail: firstname.lastname@example.org
Keywords: TRIP-Br1, autophagy, apoptosis, necroptosis, nutrient/serum starvation
Abbreviations: TRIP-Br1, Transcriptional regulator interacting with the PHD-bromodomain 1; ROS, Reactive Oxygen Species; XIAP, X-linked inhibitor of apoptosis protein; PCD, Programed cell death
Received: May 28, 2015 Accepted: August 10, 2015 Published: August 21, 2015
TRIP-Br1 oncogenic protein has been shown to have multiple biological functions in cells. In this study, we demonstrate that TRIP-Br1 functions as an oncoprotein by inhibiting autophagy, apoptosis, and necroptosis of cancer cells and eventually helping them to survive under the nutrient/serum starved condition. TRIP-Br1 expression level was significantly increased in conditions with low levels of nutrients. Nutrient depleted conditions were induced by culturing cancer cells until they were overcrowded with high cell density or in media deprived of glucose, amino acids, or serum. Among them, serum starvation significantly enhanced the expression of TRIP-Br1 only in all tested breast cancer cell lines (MCF7, MDA-MB-231, T47D, MDA-MB-435, Hs578D, BT549, and MDA-MB-435) but not in the three normal cell lines (MCF10A, HfCH8, and NIH3T3). As compared with the control cells, the introduction of TRIP-Br1 silencing siRNA into MCF7 and MDA-MB-231 cells accelerated cell death by inducing apoptosis and necroptosis. In this process, TRIP-Br1 confers resistance to serum starvation-induced cell deaths by stabilizing the XIAP protein and inhibiting cellular ROS production. Moreover, our data also show that the intracellular increase of TRIP-Br1 protein resulting from serum starvation seems to occur in part through the blockage of PI3K/AKT signaling pathway.
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