Receptor-interacting Protein Shuttles between Cell Death and Survival Signaling Pathways

Kamarajan, Pachiyappan; Bunek, Julius; Lin, Yong; Núñez, Gabriel; Kapila, Yvonne L.

doi:10.1091/mbc.e09-06-0530

Cited by 30 publications

(45 citation statements)

References 37 publications

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“…For instance, although RIP1 is not required for apoptosis induced by agonistic anti-Fas antibody or crosslinked FasL, it promotes caspase 8 activation within the receptor-associated death inducing signal complex (DISC) and apoptosis in response to membrane-bound FasL [21]. In addition, RIP1 is required for detachment-induced, Fas-mediated anoikis [22]. Inhibitor of apoptosis (IAP) antagonists are small molecule mimics that sensitize cells to apoptosis by inducing autoubiquitylation and proteasomal degradation of cIAP1 and cIAP2, and the autocrine production of TNF [23, 24].…”

Section: Rip1: a Pleiotropic Kinase Controlling Cell Survival And Celmentioning

confidence: 99%

The molecular regulation of programmed necrotic cell injury

Moquin¹,

Chan²

2010

Trends in Biochemical Sciences

138

117

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Proper regulation of cell death is essential for metazoan development and functions. Unlike apoptosis, necrosis is a more inflammatory form of cell death that might contribute to anti-viral immunity. Indeed, necrotic cell injury is distinguished from apoptosis by extensive organelle and cell swelling and plasma membrane rupture. Recent evidence indicates that an elaborate biochemical network emanating from receptors in the TNF superfamily can induce apoptosis as well as necrotic cell death. The induction of necrosis by TNF-like cytokines requires biochemical components that are distinct from those involved in apoptosis. Specifically, serine/threonine protein kinases in the receptor interacting protein (RIP) family are required for "programmed" necrotic cell injury. In this review, we discuss the molecular crosstalk between apoptosis and programmed necrosis, with a special emphasis on how caspases, protein ubiquitylation and phosphorylation regulate the induction of necrotic cell injury.

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Section: Rip1: a Pleiotropic Kinase Controlling Cell Survival And Celmentioning

confidence: 99%

The molecular regulation of programmed necrotic cell injury

Moquin¹,

Chan²

2010

Trends in Biochemical Sciences

138

117

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“…We recently showed that receptor interacting protein (RIP), shuttles between CD95/Fas death and FAK survival signaling pathways to mediate anoikis in OSCC cells 10 . Hence, under anoikis conditions, FAK and RIP dissociate, leading to the association of RIP with Fas and the formation of the death inducing signaling complex, thus enhancing apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Receptor‐interacting protein (RIP) and Sirtuin‐3 (SIRT3) are on opposite sides of anoikis and tumorigenesis

Kamarajan

Alhazzazi

Danciu

et al. 2012

Cancer

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Background Regulating crosstalk between anoikis and survival signaling pathways is crucial to regulating tissue processes and mitigating diseases like cancer. Previously, we showed that anoikis activates a CD95/Fas-mediated signaling pathway regulated by receptor-interacting protein (RIP), a kinase that shuttles between Fas-mediated cell death and integrin/FAK-mediated survival pathways. Since sirtuin-3 (SIRT3), an NAD-dependent deacetylase, is known to regulate cell survival, metabolism, and tumorigenesis, we hypothesized that SIRT3 might engage in crosstalk with Fas/RIP/integrin/FAK survival-death pathways in cancer cell systems. Methods Using immunohistochemical staining, immunoblotting, human tissue microarrays, and overexpression and suppression approaches in vitro and in vivo we examined the roles of RIP and SIRT3 in oral squamous cell carcinoma (OSCC) anoikis resistance and tumorigenesis. Results RIP and SIRT3 have an opposite expression profile in OSCC cells and tissues. Stable suppression of RIP enhances SIRT3 levels, whereas, stable suppression of SIRT3 does not impact RIP levels in OSCC cells. As OSCC cells become anoikis-resistant they form multicellular aggregates or oraspheres in suspension conditions, and their expression of SIRT3 increases as their RIP expression decreases. Also, anoikis-resistant OSCC cells with higher SIRT3 and low RIP expression induce an increased tumor burden and incidence in mice unlike their adherent OSCC cell counterparts. Furthermore, stable suppression of SIRT3 inhibits anoikis resistance and reduces tumor incidence. Conclusion RIP is a likely upstream negative regulator of SIRT3 in anoikis resistance, and an anoikis-resistant orasphere phenotype defined by higher SIRT3 and low RIP expression contributes to a more aggressive phenotype in OSCC development.

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“…We recently reported that anoikis activates a CD95/Fas-mediated signaling pathway regulated by receptor interacting protein (RIP), a kinase that shuttles between CD95/Fas-mediated cell death and integrin/FAK-mediated survival pathways in oral squamous cell carcinoma (OSCC) cells [69]. Interestingly, we found that, as OSCC cells become resistant to anoikis, their SIRT3 expression increases and their RIP expression decreases.…”

Section: Sirt3 and Cell Survivalmentioning

confidence: 99%

“…Anoikis, apoptotic cell death triggered by loss of extracellular matrix (ECM) contacts, is dysregulated in many chronic debilitating and fatal diseases, including cancer, and resistance to anoikis contributes to the development and progression of cancer [68,69,70]. We recently reported that anoikis activates a CD95/Fas-mediated signaling pathway regulated by receptor interacting protein (RIP), a kinase that shuttles between CD95/Fas-mediated cell death and integrin/FAK-mediated survival pathways in oral squamous cell carcinoma (OSCC) cells [69].…”

Section: Sirt3 and Cell Survivalmentioning

confidence: 99%

SIRT3 and cancer: Tumor promoter or suppressor?

Alhazzazi

Kamarajan

Verdin

et al. 2011

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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132

145

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Sirtuins (SIRT1 7), the mammalian homologues of the Sir2 gene in yeast, have emerging roles in age-related diseases, such as cardiac hypertrophy, diabetes, obesity, and cancer. However, the role of several sirtuin family members, including SIRT1 and SIRT3, in cancer has been controversial. The aim of this review is to explore and discuss the seemingly dichotomous role of SIRT3 in cancer biology with particular emphasis on its potential role as a tumor promoter and tumor suppressor. This review will also discuss the potential role of SIRT3 as a novel therapeutic target to treat cancer.

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Receptor-interacting Protein Shuttles between Cell Death and Survival Signaling Pathways

Abstract: RIP shuttles between CD95/Fas death and FAK survival signaling to mediate anoikis.

Cited by 30 publications

References 37 publications

The molecular regulation of programmed necrotic cell injury

The molecular regulation of programmed necrotic cell injury

Receptor‐interacting protein (RIP) and Sirtuin‐3 (SIRT3) are on opposite sides of anoikis and tumorigenesis

SIRT3 and cancer: Tumor promoter or suppressor?

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