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Yi Chuan = Hereditas Sep 2022The matrix metallopeptidase family (matrix metallopeptidase, MMPs) is a class of zinc-dependent endopeptidases that can degrade most extracellular matrices. MT1-MMP... (Review)
Review
The matrix metallopeptidase family (matrix metallopeptidase, MMPs) is a class of zinc-dependent endopeptidases that can degrade most extracellular matrices. MT1-MMP (membrane type 1 metalloprotease) is an important metallopeptidase, which is located on plasma membrane and highly expressed in most tumors. MT1-MMP promotes cancer metastasis through affecting the extracellular matrix remodeling, angiogenesis, lipid metabolism, and inflammation. However, the mechanisms of MT1-MMP in different tumors have not been fully elucidated. In this review, we summarize the latest progress and the metastasis-promoting regulatory mechanisms of MT1-MMP in different tumors, which will provide references for its in-depth research and application in the field of cancer biology.
Topics: Matrix Metalloproteinase 14; Cell Membrane
PubMed: 36384952
DOI: 10.16288/j.yczz.22-213 -
Journal of Leukocyte Biology Nov 2021Fas ligand (FasL) is best known for its ability to induce cell death in a wide range of Fas-expressing targets and to limit inflammation in immunoprivileged sites such... (Review)
Review
Fas ligand (FasL) is best known for its ability to induce cell death in a wide range of Fas-expressing targets and to limit inflammation in immunoprivileged sites such as the eye. In addition, the ability of FasL to induce a much more extensive list of outcomes is being increasingly explored and accepted. These outcomes include the induction of proinflammatory cytokine production, T cell activation, and cell motility. However, the distinct and opposing functions of membrane-associated FasL (mFasL) and the C-terminal soluble FasL fragment (sFasL) released by metalloproteinase cleavage is less well documented and understood. Both mFasL and sFasL can form trimers that engage the trimeric Fas receptor, but only mFasL can form a multimeric complex in lipid rafts to trigger apoptosis and inflammation. By contrast, a number of reports have now documented the anti-apoptotic and anti-inflammatory activity of sFasL, pointing to a critical regulatory function of the soluble molecule. The immunomodulatory activity of FasL is particularly evident in ocular pathology where elimination of the metalloproteinase cleavage site and the ensuing increased expression of mFasL can severely exacerbate the extent of inflammation and cell death. By contrast, both homeostatic and increased expression of sFasL can limit inflammation and cell death. The mechanism(s) responsible for the protective activity of sFasL are discussed but remain controversial. Nevertheless, it will be important to consider therapeutic applications of sFasL for the treatment of ocular diseases such as glaucoma.
Topics: Animals; Eye Diseases; Fas Ligand Protein; Humans; Membrane Proteins; Metalloproteases
PubMed: 33565149
DOI: 10.1002/JLB.3RI1220-834R -
Frontiers in Immunology 2023
Topics: Humans; Chronic Disease; Metalloproteases
PubMed: 37114053
DOI: 10.3389/fimmu.2023.1196791 -
International Journal of Molecular... Nov 2021Low and high temperatures are life-threatening stress factors, diminishing plant productivity. One of the earliest responses of plants to stress is a rapid burst of... (Review)
Review
Low and high temperatures are life-threatening stress factors, diminishing plant productivity. One of the earliest responses of plants to stress is a rapid burst of reactive oxygen species (ROS) in chloroplasts. Widespread efforts over the past decade shed new light on the chloroplast as an environmental sensor, translating the environmental fluctuation into varying physiological responses by utilizing distinct retrograde (chloroplast-to-nucleus) signals. Recent studies have unveiled that chloroplasts mediate a similar unfolded/misfolded/damaged protein response (cpUPR) as observed in the endoplasmic reticulum and mitochondria. Although observing cpUPR is not surprising since the chloroplast is a prime organelle producing harmful ROS, the intertwined relationship among ROS, protein damage, and chloroplast protein quality controls (cpPQCs) with retrograde signaling has recently been reported. This finding also gives rise to critical attention on chloroplast proteins involved in cpPQCs, ROS detoxifiers, transcription/translation, import of precursor proteins, and assembly/maturation, the deficiency of which compromises chloroplast protein homeostasis (proteostasis). Any perturbation in the protein may require readjustment of proteostasis by transmitting retrograde signal(s) to the nucleus, whose genome encodes most of the chloroplast proteins involved in proteostasis. This review focuses on recent findings on cpUPR and chloroplast-targeted FILAMENTOUS TEMPERATURE-SENSITIVE H proteases involved in cpPQC and retrograde signaling and their impacts on plant responses to temperature stress.
Topics: Chloroplasts; Endoplasmic Reticulum; Metalloproteases; Reactive Oxygen Species; Stress, Physiological; Temperature; Unfolded Protein Response
PubMed: 34829988
DOI: 10.3390/ijms222212106 -
Scientific Reports Mar 2022Exudate production is a natural part of the wound healing process, however levels of exudate need to be appropriately managed to maintain a moist wound environment which...
Exudate production is a natural part of the wound healing process, however levels of exudate need to be appropriately managed to maintain a moist wound environment which supports healing. An overly-exuding wound creates an environment favourable to bacterial growth. In recent years, a significant increase in commercially available superabsorbent dressings have become available which claim to absorb and retain excess exudate and its components. However, the effectiveness of these dressings in sequestering and retaining bacteria and host-derived proteins has not been compared. We have therefore investigated several superabsorbent dressings for their ability to absorb and retain bacteria (Staphylococcus aureus and Pseudomonas aeruginosa), their impact on bacterial viability, and their ability to sequester matrix metalloproteinases (MMP)-2 and 9 over 7 days. Whilst all dressings could sequester bacteria, some dressings internalised bacteria more effectively. There was considerable variation in bacterial viability within the dressings' core, as well as differences in bacterial retention. Some dressings effectively internalised and retained bacteria over time, whereas other dressings retained significantly less. These differences were reflected visually using scanning electron microscopy. Most dressings fully sequestered MMP-2 and 9. These data illustrate differences in the ability of superabsorbent dressings to absorb and retain exudate and its components.
Topics: Bandages; Exudates and Transudates; Metalloproteases; Pseudomonas aeruginosa; Wound Healing
PubMed: 35306513
DOI: 10.1038/s41598-022-08361-3 -
FASEB Journal : Official Publication of... Nov 2023Mitochondrial dysfunction plays an important role in the onset and progression of podocyte injury and proteinuria. However, the process by which the change in the...
Mitochondrial dysfunction plays an important role in the onset and progression of podocyte injury and proteinuria. However, the process by which the change in the podocyte mitochondria occurs is not well understood. Uncoupling protein 2 (UCP2) is a mitochondrial anion carrier protein, which is located in the mitochondrial inner membrane. Here, we reported that mice with podocyte-specific Ucp2 deficiency developed podocytopathy with proteinuria with aging. Furthermore, those mice exhibited increased proteinuria in experimental models evoked by Adriamycin. Our findings suggest that UCP2 mediates mitochondrial dysfunction by regulating mitochondrial dynamic balance. Ucp2-deleted podocytes exhibited increased mitochondrial fission and deficient in ATP production. Mechanistically, opacity protein 1 (OPA1), a key protein in fusion of mitochondrial inner membrane, was regulated by UCP2. Ucp2 deficiency promoted proteolysis of OPA1 by activation OMA1 which belongs to mitochondrial inner membrane zinc metalloprotease. Those finding demonstrate the role of UCP2 in mitochondrial dynamics in podocytes and provide new insights into pathogenesis associated with podocyte injury and proteinuria.
Topics: Animals; Mice; GTP Phosphohydrolases; Metalloproteases; Mitochondrial Dynamics; Mitochondrial Proteins; Podocytes; Proteinuria; Proteolysis; Uncoupling Protein 2
PubMed: 37874273
DOI: 10.1096/fj.202301055R -
Acta Crystallographica. Section D,... Nov 2022The horseshoe crab Limulus polyphemus is one of few extant Limulus species, which date back to ∼250 million years ago under the conservation of a common Bauplan...
The horseshoe crab Limulus polyphemus is one of few extant Limulus species, which date back to ∼250 million years ago under the conservation of a common Bauplan documented by fossil records. It possesses the only proteolytic blood-coagulation and innate immunity system outside vertebrates and is a model organism for the study of the evolution and function of peptidases. The astacins are a family of metallopeptidases that share a central ∼200-residue catalytic domain (CD), which is found in >1000 species across holozoans and, sporadically, bacteria. Here, the zymogen of an astacin from L. polyphemus was crystallized and its structure was solved. A 34-residue, mostly unstructured pro-peptide (PP) traverses, and thus blocks, the active-site cleft of the CD in the opposite direction to a substrate. A central `PP motif' (F-E-G-D-I) adopts a loop structure which positions Asp38 to bind the catalytic metal, replacing the solvent molecule required for catalysis in the mature enzyme according to an `aspartate-switch' mechanism. Maturation cleavage of the PP liberates the cleft and causes the rearrangement of an `activation segment'. Moreover, the mature N-terminus is repositioned to penetrate the CD moiety and is anchored to a buried `family-specific' glutamate. Overall, this mechanism of latency is reminiscent of that of the other three astacins with known zymogenic and mature structures, namely crayfish astacin, human meprin β and bacterial myroilysin, but each shows specific structural characteristics. Remarkably, myroilysin lacks the PP motif and employs a cysteine instead of the aspartate to block the catalytic metal.
Topics: Animals; Humans; Aspartic Acid; Metalloproteases; Enzyme Precursors; Catalytic Domain; Peptide Hydrolases
PubMed: 36322418
DOI: 10.1107/S2059798322009688 -
Biochimica Et Biophysica Acta.... Jan 2022The metalloproteinase meprin β plays an important role during collagen I deposition in the skin, mucus detachment in the small intestine and also regulates the... (Review)
Review
The metalloproteinase meprin β plays an important role during collagen I deposition in the skin, mucus detachment in the small intestine and also regulates the abundance of different cell surface proteins such as the interleukin-6 receptor (IL-6R), the triggering receptor expressed on myeloid cells 2 (TREM2), the cluster of differentiation 99 (CD99), the amyloid precursor protein (APP) and the cluster of differentiation 109 (CD109). With that, regulatory mechanisms that control meprin β activity and regulate its release from the cell surface to enable access to distant substrates are increasingly important. Here, we will summarize factors that alternate meprin β activity and thereby regulate its proteolytic activity on the cell surface or in the supernatant. We will also discuss cleavage of the IL-6R and TREM2 on the cell surface and compare it to CD109. CD109, as a substrate of meprin β, is cleaved within the protein core, thereby releasing defined fragments from the cell surface. At last, we will also summarize the role of proteases in general and meprin β in particular in substrate release on extracellular vesicles.
Topics: Animals; Extracellular Vesicles; Humans; Metalloendopeptidases; Proteolysis; Signal Transduction
PubMed: 34626678
DOI: 10.1016/j.bbamcr.2021.119136 -
Human Genetics Jan 2022Female infertility is a relatively common phenotype with a growing number of single gene causes although these account for only a minority of cases. Here, we report a...
Female infertility is a relatively common phenotype with a growing number of single gene causes although these account for only a minority of cases. Here, we report a consanguineous family in which adult females who are homozygous for a truncating variant in ASTL display markedly reduced fertility in a pattern strikingly similar to Astl female mice. ASTL encodes ovastacin, which is known to trigger zona pellucida hardening (ZPH) as part of the cortical reaction upon fertilization. ZPH is required for normal early embryonic development and its absence can be caused by pathogenic variants in other zona pellucida proteins that result in a similar infertility phenotype in humans and mouse. This is the first report of ASTL-related infertility in humans and suggests that the inclusion of ASTL in female infertility gene panels is warranted.
Topics: Adult; Animals; Female; Fertilization in Vitro; Humans; Infertility, Female; Metalloproteases; Mice; Mutation; Oocytes; Pedigree; Pregnancy; Zona Pellucida
PubMed: 34704130
DOI: 10.1007/s00439-021-02388-8 -
Cellular and Molecular Life Sciences :... Aug 2019Alzheimer's Disease (AD) is the sixth-leading cause of death in industrialized countries. Neurotoxic amyloid-β (Aβ) plaques are one of the pathological hallmarks in AD... (Review)
Review
Alzheimer's Disease (AD) is the sixth-leading cause of death in industrialized countries. Neurotoxic amyloid-β (Aβ) plaques are one of the pathological hallmarks in AD patient brains. Aβ accumulates in the brain upon sequential, proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretases. However, so far disease-modifying drugs targeting β- and γ-secretase pathways seeking a decrease in the production of toxic Aβ peptides have failed in clinics. It has been demonstrated that the metalloproteinase meprin β acts as an alternative β-secretase, capable of generating truncated Aβ peptides that have been described to be increased in AD patients. This indicates an important β-site cleaving enzyme 1 (BACE-1)-independent contribution of the metalloprotease meprin β within the amyloidogenic pathway and may lead to novel drug targeting avenues. However, meprin β itself is embedded in a complex regulatory network. Remarkably, the anti-amyloidogenic α-secretase a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a direct competitor for APP at the cell surface, but also a sheddase of inactive pro-meprin β. Overall, we highlight the current cellular, molecular and structural understanding of meprin β as alternative β-secretase within the complex protease web, regulating APP processing in health and disease.
Topics: ADAM10 Protein; Alzheimer Disease; Amyloid beta-Peptides; Humans; Membrane Proteins; Metalloendopeptidases; Presenilin-1; Proteolysis; Serine Endopeptidases
PubMed: 31201463
DOI: 10.1007/s00018-019-03179-1