Necroptosis, ADAM proteases and intestinal (dys)function

Heib, Michelle; Rose–John, Stefan; Adam, Dieter

doi:10.1016/bs.ircmb.2020.02.001

Cited by 7 publications

(4 citation statements)

References 427 publications

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“…Another group of cell surface metalloproteases, the ADAMs (A disintegrin and metalloproteases), is largely implicated in the shedding of protein ectodomain and paracrine signal transduction. Notably, ADAM10 and ADAM17 (TACE) play roles in gastroenterological tumors, contributing to different processes, such as a reduction in DNA damage repair, tumor growth, vascularization, and in the control of inflammatory responses in the intestine [ 90 , 91 , 92 ]. These two membrane-bound ADAM proteases can mediate the cleavage of mPD-L1 and release sPD-L1, as a 37-kDa N-terminal PD-L1 fragment, in breast cancer cell lines.…”

Section: Generation Of Soluble Pd-l1: Proteolysis and Alternative Splicingmentioning

confidence: 99%

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Bailly

Thuru

Quesnel

2021

Cancers

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Upon T-cell receptor stimulation, the Programmed cell Death-1 receptor (PD-1) expressed on T-cells can interact with its ligand PD-L1 expressed at the surface of cancer cells or antigen-presenting cells. Monoclonal antibodies targeting PD-1 or PD-L1 are routinely used for the treatment of cancers, but their clinical efficacy varies largely across the variety of tumor types. A part of the variability is linked to the existence of several forms of PD-L1, either expressed on the plasma membrane (mPD-L1), at the surface of secreted cellular exosomes (exoPD-L1), in cell nuclei (nPD-L1), or as a circulating, soluble protein (sPD-L1). Here, we have reviewed the different origins and roles of sPD-L1 in humans to highlight the biochemical and functional heterogeneity of the soluble protein. sPD-L1 isoforms can be generated essentially by two non-exclusive processes: (i) proteolysis of m/exoPD-L1 by metalloproteases, such as metalloproteinases (MMP) and A disintegrin and metalloproteases (ADAM), which are capable of shedding membrane PD-L1 to release an active soluble form, and (ii) the alternative splicing of PD-L1 pre-mRNA, leading in some cases to the release of sPD-L1 protein isoforms lacking the transmembrane domain. The expression and secretion of sPD-L1 have been observed in a large variety of pathologies, well beyond cancer, notably in different pulmonary diseases, chronic inflammatory and autoimmune disorders, and viral diseases. The expression and role of sPD-L1 during pregnancy are also evoked. The structural heterogeneity of sPD-L1 proteins, and associated functional/cellular plurality, should be kept in mind when considering sPD-L1 as a biomarker or as a drug target. The membrane, exosomal and soluble forms of PD-L1 are all integral parts of the highly dynamic PD-1/PD-L1 signaling pathway, essential for immune-tolerance or immune-escape.

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Section: Generation Of Soluble Pd-l1: Proteolysis and Alternative Splicingmentioning

confidence: 99%

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Bailly

Thuru

Quesnel

2021

Cancers

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“…The inhibition of HtrA2 by the serine protease UCF-101 alleviates DSS-induced colitis by preventing the necroptosis of intestinal epithelial cells [ 103 ]. Furthermore, an unexpected connection between necroptosis and the members of the disintegrin and metalloproteinase (ADAM) protease family is also described [ 104 ]. Indeed, murine embryonic fibroblasts derived from ADAM17 ex/ex mice fail to show the phosphorylation of MLKL and RIPK3 after TNF-induced necroptosis, suggesting a role of ADAM17 in this process [ 105 ].…”

Section: Necroptosis and Intestinal Diseasesmentioning

confidence: 99%

Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives

et al. 2020

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Necroptosis is a caspases-independent programmed cell death displaying intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development such tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis plays a role in many disease conditions and inhibiting necroptosis is currently considered a promising therapeutic strategy. In this review, we focus on the molecular mechanisms of necroptosis as well as its involvement in human diseases. We also discuss the present developing therapies that target necroptosis machinery.

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“…[99] showed that inhibition of HtrA2 by the serine protease UCF-101 alleviated DSS-induced colitis by preventing necroptosis of intestinal epithelial cells. Furthermore, an unexpected connection between necroptosis and members of the disintegrin and metalloproteinase (ADAM) protease family has been reported [100]. Hence, the disintegrin metalloprotease ADAM17, with a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17 ex/ex ) mice to dextran sulfate sodium (DSS)-induced colitis, was shown to be involved in necroptosis regulation.…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives

Negroni

Colantoni²,

Cucchiara³

et al. 2020

Preprint

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Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

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Necroptosis, ADAM proteases and intestinal (dys)function

Cited by 7 publications

References 427 publications

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives

Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives

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