TY  - JOUR
AU  - Mentrup, Torben
AU  - Loock, Ann-Christine
AU  - Fluhrer, Regina
AU  - Schröder, Bernd
TI  - Signal peptide peptidase and SPP-like proteases - Possible therapeutic targets?
JO  - Biochimica et biophysica acta / Molecular cell research
VL  - 1864
IS  - 11
SN  - 0167-4889
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DZNE-2020-05892
SP  - 2169-2182
PY  - 2017
AB  - 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.
KW  - Amino Acid Sequence: genetics
KW  - Amyloid Precursor Protein Secretases: antagonists & inhibitors
KW  - Amyloid Precursor Protein Secretases: genetics
KW  - Aspartic Acid Endopeptidases: antagonists & inhibitors
KW  - Aspartic Acid Endopeptidases: genetics
KW  - Humans
KW  - Membrane Proteins: antagonists & inhibitors
KW  - Membrane Proteins: genetics
KW  - Peptides: antagonists & inhibitors
KW  - Peptides: genetics
KW  - Peptides: metabolism
KW  - Proteolysis
KW  - Substrate Specificity
KW  - Membrane Proteins (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
KW  - dermcidin (NLM Chemicals)
KW  - Amyloid Precursor Protein Secretases (NLM Chemicals)
KW  - Aspartic Acid Endopeptidases (NLM Chemicals)
KW  - SPPL2a protein, human (NLM Chemicals)
KW  - SPPL2b protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28624439
DO  - DOI:10.1016/j.bbamcr.2017.06.007
UR  - https://pub.dzne.de/record/139570
ER  -