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@ARTICLE{Mentrup:151555,
author = {Mentrup, Torben and Cabrera-Cabrera, Florencia and Fluhrer,
Regina and Schröder, Bernd},
title = {{P}hysiological functions of {SPP}/{SPPL} intramembrane
proteases},
journal = {Cellular and molecular life sciences},
volume = {77},
number = {15},
issn = {1420-682X},
address = {Cham (ZG)},
publisher = {Springer International Publishing AG},
reportid = {DZNE-2020-01139},
pages = {2959-2979},
year = {2020},
abstract = {Intramembrane proteolysis describes the cleavage of
substrate proteins within their hydrophobic transmembrane
segments. Several families of intramembrane proteases have
been identified including the aspartyl proteases Signal
peptide peptidase (SPP) and its homologues, the SPP-like
(SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3. As
presenilin homologues, they employ a similar catalytic
mechanism as the well-studied γ-secretase. However,
SPP/SPPL proteases cleave transmembrane proteins with a type
II topology. The characterisation of SPP/SPPL-deficient
mouse models has highlighted a still growing spectrum of
biological functions and also promoted the substrate
discovery of these proteases. In this review, we will
summarise the current hypotheses how phenotypes of these
mouse models are linked to the molecular function of the
enzymes. At the cellular level, SPP/SPPL-mediated cleavage
events rather provide specific regulatory switches than
unspecific bulk proteolysis. By this means, a plethora of
different cell biological pathways is influenced including
signal transduction, membrane trafficking and protein
glycosylation.},
keywords = {Amyloid Precursor Protein Secretases: metabolism / Animals
/ Aspartic Acid Endopeptidases: chemistry / Aspartic Acid
Endopeptidases: metabolism / Humans / Membrane Proteins:
metabolism / Protein Transport / Proteolysis / Signal
Transduction / Substrate Specificity},
cin = {AG Fluhrer},
ddc = {610},
cid = {I:(DE-2719)1110000-2},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32052089},
pmc = {pmc:PMC7366577},
doi = {10.1007/s00018-020-03470-6},
url = {https://pub.dzne.de/record/151555},
}