Nutrient/serum starvation derived TRIP-Br3 down-regulation accelerates apoptosis by destabilizing XIAP

Li, Chengping; Jung, Samil; Lee, Soonduck; Jeong, Dongjun; Yang, Young; Kim, Keun-Il; Lim, Jong-Seok; Cheon, Chung-Il; Kim, Changjin; Kang, Young‐Sook

doi:10.18632/oncotarget.3112

Cited by 15 publications

(23 citation statements)

References 42 publications

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“…For example, many microRNAs suppress the translation of XIAP (32)(33)(34)(35)(36) and the E3 ligase TRIM32 degrades the XIAP protein (37). In addition, the TRIP-Br1 and TRIP-Br3 proteins inhibit the degradation of XIAP (38) and a novel mechanism for XIAP degradation through an autophagy pathway has been identified (39). Therefore, multifaceted analyses that consider these molecules are needed in order to clarify the regulation of the expression of XIAP by RPS3.…”

Section: Discussionmentioning

confidence: 99%

Ribosomal protein S3 regulates XIAP expression independently of the NF-κB pathway in breast cancer cells

et al. 2017

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The X-linked inhibitor of apoptosis (XIAP) confers the resistance of various types of cancer to standard chemotherapeutic agents such as anthracycline and taxane. In breast cancer, XIAP is known to be overexpressed. However, the mechanisms underlying the overexpression of XIAP remain currently unclear. In order to elucidate the mechanisms responsible for the overexpression of the XIAP protein in breast cancer, we attempted to clarify the mechanisms by which the natural compound curcumin downregulates XIAP in breast cancer cells. In that process, we identified the ribosomal protein S3 (RPS3) as a curcumin‑binding protein using curcumin-fixed magnetic FG beads. The knockdown of RPS3 inhibited cell growth and induced apoptosis as well as the downregulation of XIAP in breast cancer cells. Although RPS3 is known to directly bind to and activate the nuclear factor-κB (NF-κB), which induces several anti-apoptotic genes such as XIAP, the knockdown of RPS3 unexpectedly reduced the levels of the XIAP protein, but not the mRNA level of XIAP and the transcription factor NF-κB activity. These results reveal that RPS3 upregulates XIAP independently of the NF-κB pathway in human breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Ribosomal protein S3 regulates XIAP expression independently of the NF-κB pathway in breast cancer cells

et al. 2017

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“…For instance, some members of the transcriptional regulator interacting with the PHD-bromodomain (TRIP-Br) family were reported to be involved in such phenomenon. 38,39 One might suggest that D2-TGZ could disturb the molecular mechanisms responsible for this protection against apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Δ2-Troglitazone promotes cytostatic rather than pro-apoptotic effects in breast cancer cells cultured in high serum conditions

et al. 2016

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We have previously shown that D2-Troglitazone (D2-TGZ) displayed anticancer effects on breast cancer cell lines grown in low serum conditions (1% fetal calf serum (FCS)). The present study was performed in order to characterize the effects of D2-TGZ in high serum containing medium and to determine if starvation could influence the response of breast cancer cells to this compound, keeping in mind the potential interest for breast cancer therapy. We observed that in high serum conditions (10% FCS), a 48 h treatment with D2-TGZ induced a decrease in cell numbers in MDA-MB-231 and MCF-7 breast cancer cell lines. The IC 50 values were higher than in low serum conditions. Furthermore, in contrast to our previous results obtained in 1% FCS conditions, we observed that in 10% FCS-containing medium, MCF-7 cells were more sensitive to D2-TGZ than MDA-MB-231 cells. D2-TGZ also induced endoplasmic reticulum (ER) stress mainly in MDA-MB-231 cells. Besides, in high serum conditions, D2-TGZ induced a G 0 /G 1 cell cycle arrest, an inhibition of BrdU incorporation and a reduced level of cyclin D1. We observed a limited cleavage of PARP and a limited proportion of cells in sub-G 1 phase. Thus, in high serum conditions, D2-TGZ displayed cytostatic effects rather than apoptosis as previously reported in 1% FCS-containing medium. Our results are in accordance with studies suggesting that serum starvation could potentiate the action of diverse anti-cancer agents.

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“…In an effort to identify the proteins responsible for the resistance of cancer cells to nutrient starvation-derived cell death, we initially focused on the TRIP-Br1 (transcriptional regulator interacting with the PHD-bromodomain 1, also known as SERTAD1/SEI-1/p34 SEI-1 ) oncoprotein. It has attracted increasing attention because of its various important biological functions, such as the regulation of cell-cycle progression, inhibition of apoptosis, and control of transcription, as well as a critical role in tumorigenesis [ 23 – 28 ]. However, little is known about its function under conditions of nutrient starvation.…”

Section: Introductionmentioning

confidence: 99%

“…However, little is known about its function under conditions of nutrient starvation. Our previous and current studies show that TRIP-Br1 has an anti-apoptotic characteristic and its expression was significantly increased in response to nutrient/serum starvation [ 23 , 28 ]. Here, we report how TRIP-Br1 contributes to the survival of cancer cells in low-nutrient conditions during tumor growth.…”

Section: Introductionmentioning

confidence: 99%

TRIP-Br1 oncoprotein inhibits autophagy, apoptosis, and necroptosis under nutrient/serum-deprived condition

Jung

Duan

et al. 2015

Oncotarget

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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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Nutrient/serum starvation derived TRIP-Br3 down-regulation accelerates apoptosis by destabilizing XIAP

Cited by 15 publications

References 42 publications

Ribosomal protein S3 regulates XIAP expression independently of the NF-κB pathway in breast cancer cells

Ribosomal protein S3 regulates XIAP expression independently of the NF-κB pathway in breast cancer cells

Δ2-Troglitazone promotes cytostatic rather than pro-apoptotic effects in breast cancer cells cultured in high serum conditions

TRIP-Br1 oncoprotein inhibits autophagy, apoptosis, and necroptosis under nutrient/serum-deprived condition

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