1. Signal Peptide Peptidase-Type Proteases: Versatile Regulators with Functions Ranging from Limited Proteolysis to Protein Degradation
- Author
-
Marius K. Lemberg and Sara Suna Yucel
- Subjects
Proteases ,Proteolysis ,Protein degradation ,Endoplasmic Reticulum ,Regulated Intramembrane Proteolysis ,Presenilin ,03 medical and health sciences ,0302 clinical medicine ,Structural Biology ,Catalytic Domain ,medicine ,Animals ,Aspartic Acid Endopeptidases ,Humans ,Molecular Biology ,Phylogeny ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,medicine.diagnostic_test ,Chemistry ,Endoplasmic reticulum ,Cell Membrane ,Protein Transport ,Enzyme ,Biochemistry ,Signal peptide peptidase ,030217 neurology & neurosurgery - Abstract
Intramembrane proteases catalyze the unusual cleavage of peptide bonds in the plane of biological membranes. They are categorized according to their active site. The GxGD aspartyl proteases comprise presenilin, the signal peptide peptidase (SPP), and SPP-like (SPPL) proteases. Here we focus on the functionally related SPP and SPPL proteases, and review the current understanding of their substrate specificity and summarize known physiological functions in mammalian cells. We discuss how on the one hand regulated intramembrane proteolysis generates signaling molecules, and on the other hand how processes such as endoplasmic reticulum-associated degradation controls the quantity and activity of central regulators. While the enzymatic core of GxGD intramembrane proteases is conserved, association with regulatory factors and substrate adaptors may have tailored enzymes for various specific functions.
- Published
- 2020