XIAP-deficiency leads to delayed lobuloalveolar development in the mammary gland

Olayioye, Monilola A.; Kaufmann, Hitto; Pakusch, Miha; Vaux, David L.; Lindeman, Geoffrey J.; Visvader, Jane E.

doi:10.1038/sj.cdd.4401524

Cited by 59 publications

(54 citation statements)

References 12 publications

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“…93 Initial analyses showed that XIAP-deficient mice were largely normal, but only a limited number of cell types were studied and mice or cells derived from them were only challenged by a restricted set of stimuli. 94,95 As described above, the mechanisms of Fas-induced apoptosis differ substantially between different cell types, both in vitro and in vivo. Once caspase-8 is activated and processed in response to Fas ligation, it can proteolyse its specific substrates in the cytosol.…”

Section: Xiap and Type 1 Versus Type 2 Fas-induced Apoptosis Signallingmentioning

confidence: 99%

Fas death receptor signalling: roles of Bid and XIAP

2011

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Fas (also called CD95 or APO-1), a member of a subgroup of the tumour necrosis factor receptor superfamily that contain an intracellular death domain, can initiate apoptosis signalling and has a critical role in the regulation of the immune system. Fas-induced apoptosis requires recruitment and activation of the initiator caspase, caspase-8 (in humans also caspase-10), within the death-inducing signalling complex. In so-called type 1 cells, proteolytic activation of effector caspases (-3 and -7) by caspase-8 suffices for efficient apoptosis induction. In so-called type 2 cells, however, killing requires amplification of the caspase cascade. This can be achieved through caspase-8-mediated proteolytic activation of the pro-apoptotic Bcl-2 homology domain (BH)3-only protein BH3-interacting domain death agonist (Bid), which then causes mitochondrial outer membrane permeabilisation. This in turn leads to mitochondrial release of apoptogenic proteins, such as cytochrome c and, pertinent for Fas death receptor (DR)-induced apoptosis, Smac/DIABLO (second mitochondria-derived activator of caspase/direct IAP binding protein with low Pi), an antagonist of X-linked inhibitor of apoptosis (XIAP), which imposes a brake on effector caspases. In this review, written in honour of Juerg Tschopp who contributed so much to research on cell death and immunology, we discuss the functions of Bid and XIAP in the control of Fas DR-induced apoptosis signalling, and we speculate on how this knowledge could be exploited to develop novel regimes for treatment of cancer. (FasL) can induce apoptosis by a mechanism involving the adaptor protein FADD (Fas-associating protein with a novel death domain) and the proximal initiator caspase, caspase-8 (and in humans also caspase-10). Apoptosis can only be triggered by the membrane-bound form of FasL. Caspase-8 can activate the Bcl-2 homology (BH)3-only protein BH3-interacting domain death agonist (Bid), enabling a crosstalk to the intrinsic apoptotic pathway. Whereas FasL-stimulated type I cells can die independently of the intrinsic apoptotic machinery, type II cells depend on this crosstalk to mitochondria. X-linked inhibitor of apoptosis (XIAP) directly inhibits effector caspases and constitutes a discriminator between the type I and the type II Fas-induced apoptosis signalling. Besides apoptosis, Fas can trigger several non-apoptotic signalling pathways, including RIP1 kinase-dependent cell death (necroptosis), when caspase-8 is missing or disabled, as well as pathways that promote cell activation and cell proliferation. Open QuestionsHow is Fas-induced necroptosis and proliferation regulated at the molecular level? What is the role of XIAP's RING domain in Fas signalling? Why are certain Fas-expressing cell types refractory to FasL-induced killing? What are the roles of soluble FasL?The Death Receptor Fas Fas (also called CD95 or APO-1) is a member of the tumour necrosis factor receptor (TNF-R) superfamily, which also includes receptors for TNFa, TRAIL (TNF-related apoptosisinducing ligand), r...

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Section: Xiap and Type 1 Versus Type 2 Fas-induced Apoptosis Signallingmentioning

confidence: 99%

Fas death receptor signalling: roles of Bid and XIAP

2011

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“…14 Deletion of several other IAPs have demonstrated to lead to defaults in the development. XIAP deficiency delays development of the mammary gland 15 whereas that of BRUCE, a giant E3 ubiquitin ligase IAP, affects placenta development 16 and T-cell maturation. 17 How IAPs interfere with the differentiation pathways remain undetermined.…”

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confidence: 99%

Interaction of heat-shock protein 90β isoform (HSP90β) with cellular inhibitor of apoptosis 1 (c-IAP1) is required for cell differentiation

et al. 2008

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Members of the inhibitor of apoptosis protein (IAP) family have demonstrated functions in cell death, cell signalling, cell migration and mitosis. Several of them are E3 enzymes in the ubiquitination of proteins that leads to their degradation by the proteosomal machinery. We previously reported that one of them, cellular inhibitor of apoptosis protein-1 (c-IAP1), migrated from the nucleus to the surface of the Golgi apparatus in cells undergoing differentiation. Here, we show that c-IAP1 is a client protein of the stress protein HSP90b. In three distinct cellular models, the two proteins interact and migrate from the nucleus to the cytoplasm along the differentiation process through a leptomycin B-sensitive pathway. Inhibition of HSP90 proteins by small chemical molecules and specific depletion of HSP90b isoform by siRNA both lead to auto-ubiquitination of c-IAP1 and its degradation by the proteasome machinery. This chaperone function of HSP90 towards c-IAP1 is specific of its b isoform as specific depletion of HSP90a does not affect c-IAP1 content. Chemical inhibition of HSP90 or siRNA-mediated depletion of HSP90b both inhibit cell differentiation, which can be reproduced by siRNA-mediated depletion of c-IAP1. Altogether, these results suggest that HSP90b prevents auto-ubiquitination and degradation of its client protein c-IAP1, whose depletion would be sufficient to inhibit cell differentiation. Members of the inhibitor of apoptosis protein (IAP) family were initially described as a series of natural inhibitors of cell death. Among the eight human proteins of this family, X-linked IAP (XIAP) demonstrated to be the bona fide caspase inhibitor 1 whereas the others demonstrated, for the most part, functions in cell signalling 2 and mitosis. 3 Several of these proteins harbour a Really Interesting New Gene (RING) domain at the carboxy terminus and function as an E3 enzyme in the cascade of ubiquitination that targets proteins to the ubiquitinproteasome degradation machinery. 4 One of these IAP with a RING domain is cellular IAP1 (c-IAP1) that was initially described as a signalling molecule. 2 Although c-IAP1 has subsequently been described as a direct inhibitor of caspases, this remains a controversial issue. 5,6 Due to its E3 function, c-IAP1 is responsible for the ubiquitination and subsequent degradation of the adaptor protein TNF receptor associated factor 2 7 and the serinethreonine apoptosis signal-regulating kinase 1 8 in the tumour necrosis factor alpha (TNFa) signalling pathway. In this TNFa pathway, c-IAP1 was reported also to interact with the serinethreonine kinases receptor interacting protein 2 and nuclear factor kappaB (NF-kB) essential modifier, upstream of NF-kB, 9 and to block caspase-8 activation, downstream of NF-kB. 10 Deletion experiments in Drosophila melanogaster have revealed other functions of IAPs in cell differentiation, 11 cell migration, 12 and immune response. 13 In mammals, c-IAP1-deficient mice develop normally. However, cells from c-IAP1À/À mice express markedly elevated levels ...

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“…XIAP expression shows developmental patterning in the mammary gland (Olayioye et al 2005, Owens et al 2010a. In mice, XIAP mRNA and protein levels are slightly different.…”

Section: Xiap and The Mammary Glandmentioning

confidence: 99%

“…XIAP protein levels, however, are unchanged at the end of pregnancy and lactation onset but decrease on day 8 of lactation until 72 h of involution (Owens et al 2010a). In a study investigating the mammary gland in Xiap-deficient mice, defects in lobuloalveolar development were observed in late pregnancy, although normal development was apparent by day 7 of lactation allowing lactation to occur as normal (Olayioye et al 2005). Consequently, XIAP may be regarded as regulating terminal differentiation of the mammary gland.…”

Section: Xiap and The Mammary Glandmentioning

confidence: 99%

XIAP: a potential determinant of ovarian follicular fate

Phillipps¹,

Hurst²

2012

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X-linked inhibitor of apoptosis protein (XIAP), a member of the inhibitor of apoptosis protein family, is involved in regulating a number of functions including receptor-mediated intracellular signalling and early development. Its role as an endogenous caspase inhibitor, however, is the most highly characterised. Consequently, this protein has been implicated as an anti-apoptotic factor in the ovary. In vitro and in vivo studies have begun dissecting the stimuli and signalling networks that lead to XIAP upregulation in granulosa cells. The objective of this review is to briefly summarise the current knowledge concerning XIAP and its interactions with different caspases. Furthermore, XIAP's emerging role in the mammalian ovary will be explored and comparison is made with its functions in the mammary gland. Finally, the idea that XIAP may act as a molecular signalling switch in granulosa cells following detachment from underlying layers to promote follicular atresia will be introduced.

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XIAP-deficiency leads to delayed lobuloalveolar development in the mammary gland

Cited by 59 publications

References 12 publications

Fas death receptor signalling: roles of Bid and XIAP

Fas death receptor signalling: roles of Bid and XIAP

Interaction of heat-shock protein 90β isoform (HSP90β) with cellular inhibitor of apoptosis 1 (c-IAP1) is required for cell differentiation

XIAP: a potential determinant of ovarian follicular fate

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