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Signal peptide peptidase and SPP-like proteases - Possible therapeutic targets?
Mentrup T, Loock AC, Fluhrer R, Schröder B. Mentrup T, et al. Biochim Biophys Acta Mol Cell Res. 2017 Nov;1864(11 Pt B):2169-2182. doi: 10.1016/j.bbamcr.2017.06.007. Epub 2017 Jun 15. Biochim Biophys Acta Mol Cell Res. 2017. PMID: 28624439 Review.
The proteome of lysosomes.
Schröder BA, Wrocklage C, Hasilik A, Saftig P. Schröder BA, et al. Proteomics. 2010 Nov;10(22):4053-76. doi: 10.1002/pmic.201000196. Epub 2010 Oct 19. Proteomics. 2010. PMID: 20957757 Review.
Two dileucine motifs mediate late endosomal/lysosomal targeting of transmembrane protein 192 (TMEM192) and a C-terminal cysteine residue is responsible for disulfide bond formation in TMEM192 homodimers.
Behnke J, Eskelinen EL, Saftig P, Schröder B. Behnke J, et al. Biochem J. 2011 Mar 1;434(2):219-31. doi: 10.1042/BJ20101396. Biochem J. 2011. PMID: 21143193
Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes by a tyrosine motif in its C-terminal tail.
Behnke J, Schneppenheim J, Koch-Nolte F, Haag F, Saftig P, Schröder B. Behnke J, et al. FEBS Lett. 2011 Oct 3;585(19):2951-7. doi: 10.1016/j.febslet.2011.08.043. Epub 2011 Sep 2. FEBS Lett. 2011. PMID: 21896273
Foamy virus envelope protein is a substrate for signal peptide peptidase-like 3 (SPPL3).
Voss M, Fukumori A, Kuhn PH, Künzel U, Klier B, Grammer G, Haug-Kröper M, Kremmer E, Lichtenthaler SF, Steiner H, Schröder B, Haass C, Fluhrer R. Voss M, et al. J Biol Chem. 2012 Dec 21;287(52):43401-9. doi: 10.1074/jbc.M112.371369. Epub 2012 Nov 6. J Biol Chem. 2012. PMID: 23132852 Free PMC article.
In this study, we identified the 18-kDa leader peptide (LP18) of the foamy virus envelope protein (FVenv) as a new substrate for intramembrane proteolysis by human SPPL3 and SPPL2a/b. ...Moreover, the cleavage product of FVenv generated by SPPL3 serves as a new substrate f …
In this study, we identified the 18-kDa leader peptide (LP18) of the foamy virus envelope protein (FVenv) as a new substrate for intramembra …
The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain.
Schneppenheim J, Dressel R, Hüttl S, Lüllmann-Rauch R, Engelke M, Dittmann K, Wienands J, Eskelinen EL, Hermans-Borgmeyer I, Fluhrer R, Saftig P, Schröder B. Schneppenheim J, et al. J Exp Med. 2013 Jan 14;210(1):41-58. doi: 10.1084/jem.20121069. Epub 2012 Dec 24. J Exp Med. 2013. PMID: 23267015 Free PMC article.
B lymphocytes of SPPL2a(-/-) mice accumulate an N-terminal fragment (NTF) of CD74, which severely impairs membrane traffic within the endocytic system and leads to an altered response to B cell receptor stimulation, reduced BAFF-R surface expression, and accumulatio
B lymphocytes of SPPL2a(-/-) mice accumulate an N-terminal fragment (NTF) of CD74, which severely impairs membrane traffic within the
The intramembrane proteases signal Peptide peptidase-like 2a and 2b have distinct functions in vivo.
Schneppenheim J, Hüttl S, Mentrup T, Lüllmann-Rauch R, Rothaug M, Engelke M, Dittmann K, Dressel R, Araki M, Araki K, Wienands J, Fluhrer R, Saftig P, Schröder B. Schneppenheim J, et al. Mol Cell Biol. 2014 Apr;34(8):1398-411. doi: 10.1128/MCB.00038-14. Epub 2014 Feb 3. Mol Cell Biol. 2014. PMID: 24492962 Free PMC article.
Based on this, we suggested that pharmacological modulation of SPPL2a may represent a novel approach to deplete B cells in autoimmune disorders. ...We demonstrate that in vivo SPPL2b does not exhibit a physiologically relevant contribution to CD74 proteolysis in B a …
Based on this, we suggested that pharmacological modulation of SPPL2a may represent a novel approach to deplete B cells in autoimmune …
Signal-peptide-peptidase-like 2a is required for CD74 intramembrane proteolysis in human B cells.
Schneppenheim J, Hüttl S, Kruchen A, Fluhrer R, Müller I, Saftig P, Schneppenheim R, Martin CL, Schröder B. Schneppenheim J, et al. Biochem Biophys Res Commun. 2014 Aug 15;451(1):48-53. doi: 10.1016/j.bbrc.2014.07.051. Epub 2014 Jul 15. Biochem Biophys Res Commun. 2014. PMID: 25035924 Free PMC article.
Nevertheless, inhibition of SPPL2a has been suggested as novel approach to target B cells for treating autoimmunity. Here, we characterize human B cell lines with a homozygous microdeletion on chromosome 15. ...By this means, we present evidence that the role of SPP …
Nevertheless, inhibition of SPPL2a has been suggested as novel approach to target B cells for treating autoimmunity. Here, we charact …
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