%0 Journal Article
%A Mentrup, Torben
%A Loock, Ann-Christine
%A Fluhrer, Regina
%A Schröder, Bernd
%T Signal peptide peptidase and SPP-like proteases - Possible therapeutic targets?
%J Biochimica et biophysica acta / Molecular cell research
%V 1864
%N 11
%@ 0167-4889
%C Amsterdam [u.a.]
%I Elsevier
%M DZNE-2020-05892
%P 2169-2182
%D 2017
%X Signal peptide peptidase (SPP) and the four homologous SPP-like proteases SPPL2a, SPPL2b, SPPL2c and SPPL3 are GxGD-type intramembrane-cleaving proteases (I-CLIPs). In addition to divergent subcellular localisations, distinct differences in the mechanistic properties and substrate requirements of individual family members have been unravelled. SPP/SPPL proteases employ a catalytic mechanism related to that of the γ-secretase complex. Nevertheless, differential targeting of SPP/SPPL proteases and γ-secretase by inhibitors has been demonstrated. Furthermore, also within the SPP/SPPL family significant differences in the sensitivity to currently available inhibitory compounds have been reported. Though far from complete, our knowledge on pathophysiological functions of SPP/SPPL proteases, in particular based on studies in mice, has been significantly increased over the last years. Based on this, inhibition of distinct SPP/SPPL proteases has been proposed as a novel therapeutic concept e.g. for the treatment of autoimmunity and viral or protozoal infections, as we will discuss in this review. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.
%K Amino Acid Sequence: genetics
%K Amyloid Precursor Protein Secretases: antagonists & inhibitors
%K Amyloid Precursor Protein Secretases: genetics
%K Aspartic Acid Endopeptidases: antagonists & inhibitors
%K Aspartic Acid Endopeptidases: genetics
%K Humans
%K Membrane Proteins: antagonists & inhibitors
%K Membrane Proteins: genetics
%K Peptides: antagonists & inhibitors
%K Peptides: genetics
%K Peptides: metabolism
%K Proteolysis
%K Substrate Specificity
%K Membrane Proteins (NLM Chemicals)
%K Peptides (NLM Chemicals)
%K dermcidin (NLM Chemicals)
%K Amyloid Precursor Protein Secretases (NLM Chemicals)
%K Aspartic Acid Endopeptidases (NLM Chemicals)
%K SPPL2a protein, human (NLM Chemicals)
%K SPPL2b protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28624439
%R 10.1016/j.bbamcr.2017.06.007
%U https://pub.dzne.de/record/139570