Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis

Edison, Natalia; Curtz, Yael; Paland, Nicole; Mamriev, Dana; Chorubczyk, Nicolas; Haviv-Reingewertz, Tali; Kfir, Nir; Morgenstern, David; Kupervaser, Meital; Kagan, Juliana; Kim, Hyoung Tae; Larisch, Sarit

doi:10.1016/j.celrep.2017.09.052

Cited by 74 publications

(80 citation statements)

References 58 publications

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“…Recent studies have reported that ARTS can combine with BCL-2 to form a XIAP-ARTS-Bcl-2 complex. Through the E3 ubiquitin ligase function of XIAP, the complex can mediate the degradation of Bcl-2 through the ubiquitin proteasome pathway to promote apoptosis [16]. To clarify the mechanism of Septin4 in promoting the apoptosis of tumor cells, we found that Septin4 can interact with BAX and enhance this interaction following stimulation with DOX ( Figure 5).…”

Section: Discussionmentioning

confidence: 97%

“…Septin4 is the most important XIAP antagonist proteins, located in the outer mitochondrial membrane [11][12][13][14]. When apoptosis occurs, spetin4 can translocate from the mitochondria to cytoplasm and directly bind to XIAP, thus activating caspases and leading to cell death [15,16]. Moreover, unlike traditional tumor suppressors or oncogenes, whose loss-or gain-of-function mutations can lead to the occurrence of cancer [17], Septin4 can affect tumor occurrence through expression changes, which makes it a more universal cancer suppressor.…”

Section: Introductionmentioning

confidence: 99%

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Septin4 promotes cell death in human colon cancer cells by interacting with BAX

Zhao¹,

Feng²,

Wang³

et al. 2020

Int. J. Biol. Sci.

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Septin4 is a tumor suppressor protein that promotes cell programmed death in various cell types through specifically antagonizing XIAP (X linked inhibitor of apoptosis), little is known its other novel binding partner and role in colorectal cancer. In this study, we found that Septin4 significantly expressed lower in human colon cancer when compared to peri-tumor benign cells, and its low expression was significantly associated with worse prognostic outcomes. Furthermore, Septin4 participated in DOX-induced colon cancer cell death in vitro. Septin4-overexpressing colon cancer cells displayed augmented apoptotic cell death and ROS production. Additionally, Septin4-knockdown cells revealed a resistance of DOX-induced cell death and reduced ROS production. Importantly, we first identified that BAX is a novel Septin4 binding partner and the interaction is enhanced under DOX treatment. Finally, Septin4-knockdown promoted colon cells growth in vivo. These observations suggest that Septin4 as an essential molecule contribute to the occurrence and development of human colon cancer and provide new technical approaches for targeted treatment of this disease.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Septin4 promotes cell death in human colon cancer cells by interacting with BAX

Zhao¹,

Feng²,

Wang³

et al. 2020

Int. J. Biol. Sci.

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“…miR-185 regulates the Bcl-2 family to promote the sensitivity of nasopharyngeal carcinoma cells to radiation. Bcl-2 is an apoptosis-inhibiting gene, and at least 19 homologs have been discovered, which play a regulatory role in the mitochondrial-dependent apoptotic pathway and control the release of cytochrome c and other apoptotic factors in mitochondria [46,47]. Members of the Bcl-2 family contain 1-4 Bcl-2 homology domains (BH1-4), of which BH4 is a domain unique to anti-apoptotic proteins, and BH3 is a domain involved in promoting apoptosis.…”

Section: Mirnas Participate In Radiotherapy Resistance Of Nasopharyngmentioning

confidence: 99%

MiRNAs in Radiotherapy Resistance of Nasopharyngeal Carcinoma

Tian¹,

Tang²,

Yi³

et al. 2020

J. Cancer

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Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck in Southeast Asia and southern China. Although the comprehensive treatment based on intensity-modulated radiation therapy improves outcomes, the five-year survival rate of NPC patients is low, and the recurrence remains high. Radiotherapy resistance is the main cause of poor prognosis in NPC patients. MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs regulating various biological functions in eukaryotes. These miRNAs can regulate the development and progression of nasopharyngeal carcinoma by affecting the proliferation, apoptosis, movement, invasion and metastasis of NPC cells. The abnormal expression of miRNAs is closely related to radiotherapy sensitivity and prognosis of NPC patients, which can affect the transmission of related signaling pathways by regulating the expression of tumor suppressor genes and / or oncogenes, and therefore participate in radiotherapy resistance in nasopharyngeal carcinoma. Here, we review the mechanisms by which miRNAs may be involved in the radiotherapy resistance of nasopharyngeal carcinoma.

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“…ARTS binds to p53 without affecting p53 protein stability ARTS has been documented as a key pro-apoptotic protein (Larisch et al, 2000 acting by targeting XIAP (Gottfried et al, 2004, Garrison et al, 2011 and Bcl-2 (Edison et al, 2017). Thus, we sought to explore if ARTS plays a role in p53-associated apoptotic pathway, since it is a p53-inducible gene.…”

Section: Arts Expression Is Induced By P53 In Cancer Cellsmentioning

confidence: 99%

“…ARTS initiates caspase activation upstream of mitochondria by directly binding and degrading XIAP (X-linked inhibitor of apoptosis) via the ubiquitin proteasome system (UPS) (Gottfried et al, 2004, Garrison et al, 2011. Recently, ARTS was shown to induce ubiquitination and degradation of Bcl-2 by bridging the E3-ubiquitin ligase XIAP to Bcl-2 (Edison et al, 2017). Studies in human and mice have shown that ARTS functions as a tumor suppressor protein (Elhasid et al, 2004, Kissel et al, 2005, Garcia-Fernandez et al, 2010, Fuchs et al, 2013, Koren et al, 2018.…”

Section: Introductionmentioning

confidence: 99%

p53 induces ARTS to promote mitochondrial apoptosis

Hao

Chen

Liao

et al. 2020

Preprint

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Apoptosis Related protein in TGF-β Signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-β, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here, we identified the pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 and a variety of p53-inducing agents increased both mRNA and protein levels of ARTS, whereas ablation of p53 reduced ARTS expression in response to multiple stress conditions. Also, γ-irradiation induced p53-dependent ARTS expression in mice. Consistently, p53 binds to the responsive DNA element on the ARTS promoter and transcriptionally activated the promoter-driven expression of a luciferase reporter gene.Interestingly, ARTS binds to and sequesters p53 at mitochondria, enhancing the interaction of the latter with Bcl-XL. Ectopic ARTS markedly augments DNA damage stress-or Nutlin-3-triggered apoptosis, while ablation of ARTS preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that ARTS collaborates with p53 in mitochondria-engaged apoptosis.

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Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis

Cited by 74 publications

References 58 publications

Septin4 promotes cell death in human colon cancer cells by interacting with BAX

Septin4 promotes cell death in human colon cancer cells by interacting with BAX

MiRNAs in Radiotherapy Resistance of Nasopharyngeal Carcinoma

p53 induces ARTS to promote mitochondrial apoptosis

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