Journal Article (Review Article)

DZNE-2020-05892

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Signal peptide peptidase and SPP-like proteases - Possible therapeutic targets?

Mentrup, T. ; Loock, A.-C. ; Fluhrer, R.DZNE* ; Schröder, B. (Corresponding author)

2017
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.bbamcr.2017.06.007

Abstract: 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.

Keyword(s): Amino Acid Sequence: genetics (MeSH) ; Amyloid Precursor Protein Secretases: antagonists & inhibitors (MeSH) ; Amyloid Precursor Protein Secretases: genetics (MeSH) ; Aspartic Acid Endopeptidases: antagonists & inhibitors (MeSH) ; Aspartic Acid Endopeptidases: genetics (MeSH) ; Humans (MeSH) ; Membrane Proteins: antagonists & inhibitors (MeSH) ; Membrane Proteins: genetics (MeSH) ; Peptides: antagonists & inhibitors (MeSH) ; Peptides: genetics (MeSH) ; Peptides: metabolism (MeSH) ; Proteolysis (MeSH) ; Substrate Specificity (MeSH) ; Membrane Proteins ; Peptides ; dermcidin ; Amyloid Precursor Protein Secretases ; Aspartic Acid Endopeptidases ; SPPL2a protein, human ; SPPL2b protein, human

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Contributing Institute(s):

1. Signal Peptide Peptidases as Models for γ-Secretase (AG Fluhrer)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2017

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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