Amplification of apoptosis through sequential caspase cleavage of the MET tyrosine kinase receptor

Foveau, Bénédicte; Leroy, Catherine; Ancot, Frédéric; Deheuninck, Julien; Ji, Zongling; Fafeur, Véronique; Tulasne, David

doi:10.1038/sj.cdd.4402080

Cited by 60 publications

(65 citation statements)

References 36 publications

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“…The main hypothesis with regard to the role of ligand binding is inhibition of the caspase cleavage. This hypothesis has been partly confirmed for some DRs, UNC5H2 (Tanikawa et al, 2003), TrkC (Tauszig-Delamasure et al, 2007), EphA4 (Furne et al, 2009) and MET (Tulasne et al, 2004;Foveau et al, 2007). For other receptors, the effect of ligand on caspase cleavage cannot be assessed because cleavage products have relatively short half-lives and are thus hardly detectable in vivo.…”

Section: Role Of Ligand Bindingmentioning

confidence: 94%

“…DCC, neogenin, Ptc, ALK, EphA4 are cleaved once, roughly in the middle of their intracellular domain (Mehlen et al, 1998;Thibert et al, 2003;Matsunaga et al, 2004;Mourali et al, 2006;Furne et al, 2009). The cleavage site of UNC5 receptors is very close to the plasma membrane (Llambi et al, 2001), whereas RET, Trkc and MET have two cleavage sites A new paradigm in cell signaling and cancer therapy D Goldschneider and P Mehlen (Bordeaux et al, 2000;Foveau et al, 2007;TauszigDelamasure et al, 2007). The cases of p75 NTR and integrins are less clear, as there is no solid evidence that caspase cleavage is needed for their proapoptotic effect.…”

Section: Drs Are Caspase Substratesmentioning

confidence: 99%

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Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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Section: Role Of Ligand Bindingmentioning

confidence: 94%

Section: Drs Are Caspase Substratesmentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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“…Under stress conditions, the MET cytoplasmic portion undergoes sequential cleavage by caspases, first at an aspartic acid residue in the carboxy-terminal end (Asp1374) and then at a second aspartic acid in the juxtamembrane portion (Asp1000) (see the figure, part b). This yields an intracellular soluble fragment, which is comprised of the kinase domain and triggers cell death 162,163 . Notably, if stress induction is accompanied by HGF stimulation, caspase activation is reduced and generation of the intracellular pro-apoptotic fragment is prevented 162 .…”

Section: Competing Interests Statementmentioning

confidence: 99%

MET signalling: principles and functions in development, organ regeneration and cancer

Trusolino

Bertotti

Comoglio

2010

Nat Rev Mol Cell Biol

1,083

1,076

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The MET tyrosine kinase receptor (also known as the HGF receptor) promotes tissue remodelling, which underlies developmental morphogenesis, wound repair, organ homeostasis and cancer metastasis, by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations. The versatility of MET-mediated biological responses is sustained by qualitative and quantitative signal modulation. Qualitative mechanisms include the engagement of dedicated signal transducers and the subcellular compartmentalization of MET signalling pathways, whereas quantitative regulation involves MET partnering with adaptor amplifiers or being degraded through the shedding of its extracellular domain or through intracellular ubiquitylation. Controlled activation of MET signalling can be exploited in regenerative medicine, whereas MET inhibition might slow down tumour progression.Throughout embryogenesis, cells bud off from developing tissues and move outwards to shape and pattern the complex architecture of prospective organs 1 . A similar process occurs in adult life during wound healing and tissue repair, when lingering cells migrate into injury sites to recreate the pre-existing structures 2 . The acquisition of cell motility is necessary, but not sufficient, for this event. Cells that detach from their neighbours must elude anoikis, a form of apoptotic cell death that occurs when cells lose adhesion with the extracellular matrix 3 . Moreover, migratory cells undergo extensive mitotic divisions to produce 'founder populations', which settle in newly forming organs during development or colonize worn tissues during repair 4,5 . The normal phases of embryogenesis and organ regeneration strongly resemble the pathological process of tumour invasiveness: similarly to cells at the wound edge, cells at the tumour's leading front disrupt intercellular contacts and infiltrate the adjacent surroundings, where they resist anoikis and grow before lodging in the blood vessels for systemic dissemination 6 . This resemblance is not simply a biological correlate, it has a common mechanistic basis: cancer cells resurrect the latent schemes of cellular reorganization, which are usually confined to embryonic development and damaged adult organs, and leverage them to become competent for metastasization 7 . The activities -motility, survival and proliferation -that occur in developing, injured and neoplastic tissues embody a biological programme that is defined as 'invasive growth' 8 . This is triggered by extracellular stimuli that regulate the activity of several transcription factors that, in turn, modulate the expression of a number of proteins, ranging from cytoskeletal and cell-cell junctional components to cell cycle regulators and anti-apoptotic effectors 9, 10 . One major environmental inducer of invasive growth is hepatocyte growth factor (HGF, also known as scatter factor), the ligand for the MET tyrosine kinase receptor (also known as the HGF receptor) 11,12,13,14,15,16,17,18,19,20 (Box 1). ...

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“…Assessment of caspase-cleavage was as previously described. 45 Briefly, 3 × 10 5 HeLa cells/well were distributed in 6 wellplates. After 24 h, cells were lysed in 80 μl of the lysis buffer (20 mM Pipes pH7.2, 100 mM NaCl, 1% Chaps, 10% Sucrose+5 mMDTT+50 μM EDTA).…”

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confidence: 99%

Caspases shutdown nonsense-mediated mRNA decay during apoptosis

et al. 2015

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Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance mechanism that plays integral roles in eliminating mRNAs with premature termination codons to prevent the synthesis of truncated proteins that could be pathogenic. One response to the accumulation of detrimental proteins is apoptosis, which involves the activation of enzymatic pathways leading to protein and nucleic acid cleavage and culminating in cell death. It is not clear whether NMD is required to ensure the accurate expression of apoptosis genes or is no longer necessary since cytotoxic proteins are not an issue during cell death. The present study shows that caspases cleave the two NMD factors UPF1 and UPF2 during apoptosis impairing NMD. Our results demonstrate a new regulatory pathway for NMD that occurs during apoptosis and provide evidence for role of the UPF cleaved fragments in apoptosis and NMD inhibition.

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Amplification of apoptosis through sequential caspase cleavage of the MET tyrosine kinase receptor

Cited by 60 publications

References 36 publications

Dependence receptors: a new paradigm in cell signaling and cancer therapy

Dependence receptors: a new paradigm in cell signaling and cancer therapy

MET signalling: principles and functions in development, organ regeneration and cancer

Caspases shutdown nonsense-mediated mRNA decay during apoptosis

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