IAPs: Guardians of RIPK1

Darding, Maurice; Meier, Pascal

doi:10.1038/cdd.2011.163

Cited by 97 publications

(80 citation statements)

References 84 publications

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“…The IAP family regulates cell survival and members of this family are often deregulated in cancer, which may be a factor for chemoresistance and treatment failure [28]. In most normal adult tissues, Survivin expression is very low or undetectable [21,29,30].…”

Section: Discussionmentioning

confidence: 99%

Exosomes Secreted from Human Cancer Cell Lines Contain Inhibitors of Apoptosis (IAP)

Valenzuela

Bennit

Gonda

et al. 2015

Cancer Microenvironment

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Exosomes are endosomal-derived nanovesicles released by normal and tumor cells which have been shown to transfer functionally active protein, lipids, mRNAs and miRNAs between cells. Varying in molecular profiles, biological roles, functional roles and protein contents, exosomes have been described as Bmulti-purpose carriers^playing a role in supporting the survival and growth of tumor cells. The IAP Survivin has been found to be present in tumor exosomes. However, the existence of other IAPs in tumor exosomes is still unknown. Survivin, cIAP1, cIAP2 and XIAP mRNA and protein are differently expressed in a panel of tumor cell lines: DLCL2, HeLa, MCF-7, Panc-1, and PC3. Exosomes were isolated from conditioned media collected from the cells from which RNA and protein were extracted. Our results provide evidence that like Survivin, XIAP, cIAP1 and cIAP2 proteins are found in tumor exosomes. The mRNA expression, however, is differentially expressed across the tumor cell lines. The presence of these bioactive molecules in exosomes may not only serve as warning signals, but also play a role in providing protection to the cancer cells against changes that are constantly occurring in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Exosomes Secreted from Human Cancer Cell Lines Contain Inhibitors of Apoptosis (IAP)

Valenzuela

Bennit

Gonda

et al. 2015

Cancer Microenvironment

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“…42 Although it is clear that IAPs are frequently deregulated in cancer, less clear is how they exert their pro-tumorigenic effect. Recent data suggest that the E3 ubiquitine ligase activity of IAPs directly influence the assembly of a large death-inducing platform called "ripoptosome" 43 by acting on the stability of the RIP1 kinase. Ripoptosome contains the core components RIP1, FADD and caspase-8 and assembles in response to genotoxic stress-induced depletion of at least two members among XIAP, cIAP1 and cIAP2.…”

Section: Discussionmentioning

confidence: 99%

ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways

et al. 2012

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“…These kinases take part in the formation of the apoptotic macromolecular platform leading to the activation of caspases or guide the activation of necrosis in the presence of caspase inhibition (Darding and Meier, 2012). Indeed among the recent findings concerning the regulation of programmed cell death is the discovery of the ripoptosome in mammals, a death receptor/ ligand independent macromolecular platform build up by the core components RIP1, caspase-8 and FADD.…”

Section: Conservation Of the Extrinsic Apoptotic Pathwaymentioning

confidence: 99%

Hydra, a versatile model to study the homeostatic and developmental functions of cell death

Reiter¹,

Crescenzi²,

Galliot³

et al. 2012

Int. J. Dev. Biol.

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In the freshwater cnidarian polyp Hydra, cell death takes place in multiple contexts. Indeed apoptosis occurs during oogenesis and spermatogenesis, during starvation, and in early head regenerating tips, promoting local compensatory proliferation at the boundary between heterografts. Apoptosis can also be induced upon exposure to pro-apoptotic agents (colchicine, wortmannin), upon heat-shock in the thermosensitive sf-1 mutant, and upon wounding. In all these contexts, the cells that undergo cell death belong predominantly to the interstitial cell lineage, whereas the epithelial cells, which are rather resistant to pro-apoptotic signals, engulf the apoptotic bodies. Beside this clear difference between the interstitial and the epithelial cell lineages, the different interstitial cell derivatives also show noticeable variations in their respective apoptotic sensitivity, with the precursor cells appearing as the most sensitive to pro-apoptotic signals. The apoptotic machinery has been well conserved across evolution. However, its specific role and regulation in each context are not known yet. Tools that help characterize apoptotic activity in Hydra have recently been developed. Among them, the aposensor Apoliner initially designed in Drosophila reliably measures wortmannin-induced apoptotic activity in a biochemical assay. Also, flow cytometry and TUNEL analyses help identify distinctive features between wortmannin-induced and heat-shock induced apoptosis in the sf-1 strain. Thanks to the live imaging tools already available, Hydra now offers a model system with which the functions of the apoptotic machinery to maintain long-term homeostasis, stem cell renewal, germ cell production, active developmental processes and non-self response can be deciphered. KEY WORDS: apoptosis, aposensor, DNA fragmentation, caspase inhibitors, flow cytometry Apoptosis occurs in multiple contexts in HydraNew advances in the field of cell death continuously contribute to show the deep intricacy of the apoptotic machinery with a variety of cell behaviors and developmental processes (Yi and Yuan, 2009;Fuchs and Steller, 2011;Miura, 2011). Indeed knockout and knockdown based studies performed in well-established model organisms such as nematodes, flies and mice provided us with detailed information about the molecular actors that guide the interactions between cell death and cell survival, cell death and cell proliferation, cell death and cell differentiation. However these model systems despite their fabulous genetic potency provide restricted conditions to study these interactions (Podrabsky and Krumschnabel, 2010). Therefore, given the conservation of the apoptotic machinery since basal metazoans (Srivastava et al., 2010) and the multiple impact of cell death in complex cellular and developmental processes, there is a need to extend our focus Int. J. Dev. Biol. 56: 593-604 (2012) doi: 10.1387/ijdb.123499sr Abbreviations used in this paper: AO, acridine orange; APAF1, apoptotic protease activating factor 1; Bcl-2, B-cell lymph...

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IAPs: Guardians of RIPK1

Cited by 97 publications

References 84 publications

Exosomes Secreted from Human Cancer Cell Lines Contain Inhibitors of Apoptosis (IAP)

Exosomes Secreted from Human Cancer Cell Lines Contain Inhibitors of Apoptosis (IAP)

ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways

Hydra, a versatile model to study the homeostatic and developmental functions of cell death

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