Requirements for Signal Peptide Peptidase-Catalyzed Intramembrane Proteolysis

Molecular insights into mechanisms of intramembrane proteolysis through signal peptide peptidase (SPP).

The processing of membrane-anchored signalling molecules and transcription factors by RIP (regulated intramembrane proteolysis) is a major signalling paradigm in eukaryotic cells. Intramembrane cleaving proteases liberate fragments from membrane-bound precursor proteins which typically fulfil functions such as cell signalling and regulation, immunosurveillance and intercellular communication. F...

Intramembrane Proteolysis of Signal

Intramembrane-cleaving aspartic proteases and disease: presenilins, signal peptide peptidase and their homologs.

Recent studies demonstrate that presenilins (PSs) and signal peptide peptidase (SPP) are members of a novel protease family of integral membrane proteins that may utilize a catalytic mechanism similar to classic aspartic proteases such as pepsin, renin and cathepsin D. The defining features of the PSs and SPP are their ability to cleave substrate polypeptides within a transmembrane region, the ...

The intramembrane proteases signal Peptide peptidase-like 2a and 2b have distinct functions in vivo.

We reported recently that the presenilin homologue signal peptide peptidase-like 2a (SPPL2a) is essential for B cell development by cleaving the N-terminal fragment (NTF) of the invariant chain (li, CD74). Based on this, we suggested that pharmacological modulation of SPPL2a may represent a novel approach to deplete B cells in autoimmune disorders. With regard to reported overlapping substrate ...

Intramembrane proteolysis and post-targeting functions of signal peptides.

Signal sequences are the addresses of proteins destined for secretion. In eukaryotic cells, they mediate targeting to the endoplasmic reticulum membrane and insertion into the translocon. Thereafter, signal sequences are cleaved from the pre-protein and liberated into the endoplasmic reticulum membrane. We have recently reported that some liberated signal peptides are further processed by the i...