TRIP-Br1 oncoprotein inhibits autophagy, apoptosis, and necroptosis under nutrient/serum-deprived condition.
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.
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Samil
S
Jung
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Chengping
C
Li
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Jingjing
J
Duan
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Soonduck
S
Lee
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Kyeri
K
Kim
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Yeonji
Y
Park
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Young
Y
Yang
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Keun-Il
KI
Kim
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Jong-Seok
JS
Lim
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Chung-Il
CI
Cheon
College of Pharmacy, Sookmyung Women's University, Seoul, 140-742, South Korea.
Young-Sook
YS
Kang
Department of Life Systems, Sookmyung Women's University, Seoul, 140-742, South Korea.
Myeong-Sok
MS
Lee
D000596:Amino Acids / Q000172:deficiency*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D016895:Culture Media, Serum-Free / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D041681:NIH 3T3 Cells; D009336:Necrosis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D000596:Amino Acids; D016895:Culture Media, Serum-Free; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; C402464:SERTAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
TRIP-Br1; apoptosis; autophagy; necroptosis; nutrient/serum starvation