ArticleThe Biochemical journal2007
Presenilin/gamma-secretase and alpha-secretase-like peptidases cleave human MHC Class I proteins.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- An interactive network of elastase, secretases, and PAR-2 protein regulates CXCR1 receptor surface expression on neutrophils.The Journal of biological chemistry · 2014Trial
- Discovery of Potent and Selective Inhibitors against Protein-Derived Electrophilic Cofactors.Journal of the American Chemical Society · 2022Article
- Merkel Cell Polyomavirus and Merkel Cell Carcinoma.Cancers · 2020Review
- Proteolytic Processing of Neuregulin 2.Molecular neurobiology · 2020Article
- Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness.PLoS pathogens · 2018Article
- Proteomic changes in cerebrospinal fluid from primary central nervous system lymphoma patients are associated with protein ectodomain shedding.Oncotarget · 2017Article
- SheddomeDB: the ectodomain shedding database for membrane-bound shed markers.BMC bioinformatics · 2017Review
- Loss of Presenilin 2 Function Is Associated with Defective LPS-Mediated Innate Immune Responsiveness.Molecular neurobiology · 2016Article
- MHC class I limits hippocampal synapse density by inhibiting neuronal insulin receptor signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Rapid temporal dynamics of transcription, protein synthesis, and secretion during macrophage activation.Molecular & cellular proteomics : MCP · 2014Article
- Alzheimer's disease and HLA-A2: linking neurodegenerative to immune processes through an in silico approach.BioMed research international · 2014Article
- Metalloproteinases and their natural inhibitors in inflammation and immunity.Nature reviews. Immunology · 2013Review
- Matrix metalloproteinase-2 (MMP-2) generates soluble HLA-G1 by cell surface proteolytic shedding.Molecular and cellular biochemistry · 2013Article
- BACE1 and presenilin/γ-secretase regulate proteolytic processing of KCNE1 and 2, auxiliary subunits of voltage-gated potassium channels.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- The many substrates of presenilin/γ-secretase.Journal of Alzheimer's disease : JAD · 2011Review
- Presenilin 2 is the predominant γ-secretase in microglia and modulates cytokine release.PloS one · 2010Article
- Trafficking of receptor tyrosine kinases to the nucleus.Experimental cell research · 2009Review
- The autonomous notch signal pathway is activated by baicalin and baicalein but is suppressed by niclosamide in K562 cells.Journal of cellular biochemistry · 2009Article
- Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements.PLoS biology · 2008Article
- gamma-Secretase: a multifaceted regulator of angiogenesis.Journal of cellular and molecular medicine · 2008Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HLA (human leucocyte antigen)-A2 is an MHC Class I protein with primary functions in T-cell development and initi-ation of immune cell responses. MHC I proteins also play roles in intercellular adhesion, apoptosis, cell proliferation and neuronal plasticity. By utilizing a sequence comparison analysis, we recently identified HLA-A2 as a potential substrate for the Alzheimer's disease-associated PS1 (presenilin 1)/gamma-secretase. alpha-Secretase-like membrane metalloproteinases are responsible for an initial shedding event, partially mediated by ADAM (a disinteg-rin and metalloproteinase)-10. Accordingly, activation or inhibition of alpha-secretase-like membrane metalloproteinases directly modulated levels of a 14 kDa HLA-A2 CTF (C-terminal frag-ment) in CHO (Chinese-hamster ovary) cells. To show that the HLA-A2 CTF is subsequently cleaved by PS1/gamma-secretase, we re-duced its activity in cell lines stably expressing HLA-A2 and in Jurkat T-cells expressing endogenous MHC I. Treatment with specific PS1/gamma-secretase inhibitors or expression of a dominant-negative construct led to a significant accumulation of HLA-A2 CTFs. We also identified the PS1/gamma-secretase cleavage product of HLA-A2 CTF, termed HLA-A2 intracellular domain, in cell-free and cell-based experiments. In the absence of proteasome inhibitors, HLA-A2 intracellular domain underwent rapid degrad-ation. These data indicate that MHC I proteins undergo extra-cellular domain cleavage mediated by alpha-secretases and the cleavage product is subsequently cleaved by PS1/gamma-secretase.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.