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of or relating to proteolysis

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1. 外傷に伴う凝固障害 coagulopathy associated with trauma
2. A群レンサ球菌：病原性因子および発症機序 group a streptococcus virulence factors and pathogenic mechanisms
3. 炭疽菌の微生物学、病因、および疫学 microbiology pathogenesis and epidemiology of anthrax
4. 皮質下梗塞および白質脳症を伴う常染色体優性脳動脈症（CADASIL） cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy cadasil
5. Prothrombin G20210A mutation

English Journal

Differential protein-protein interactions of full length human FasL and FasL fragments generated by proteolysis.

Lettau M1, Voss M2, Ebsen H3, Kabelitz D4, Janssen O5.Author information 1Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Building 17, D-24105 Kiel, Germany. Electronic address: lettau@immunologie.uni-kiel.de.2Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Building 17, D-24105 Kiel, Germany. Electronic address: Matthias.Voss@dzne.lmu.de.3Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Building 17, D-24105 Kiel, Germany. Electronic address: Henriette.Oberdoerster@uksh.de.4Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Building 17, D-24105 Kiel, Germany. Electronic address: Dietrich.Kabelitz@uksh.de.5Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, Building 17, D-24105 Kiel, Germany. Electronic address: Ottmar.Janssen@uksh.de.AbstractFas ligand (FasL) is a death factor of the tumor necrosis factor superfamily. Like other members of this family of type II transmembrane proteins, FasL is subject to ectodomain shedding by a disintegrin and metalloproteinases (ADAMs) liberating soluble FasL and leaving membrane-integral N-terminal fragments (NTFs). These NTFs are further processed by intramembrane proteolysis through signal peptide peptidase-like 2a (SPPL2a), releasing intracellular domains (ICDs) which might translocate to the nucleus to regulate transcription. Previous work established that the proline-rich domain within the cytosolic N-terminus of FasL is required for protein-protein interactions with different Src homology 3 (SH3) or WW domain proteins. Distinct binding partners regulate FasL storage and surface appearance or are involved in other aspects of FasL biology. Given the large number of FasL interactors, we asked whether proteolytically processed FasL fragments associate with the same or distinct sets of SH3 domain proteins. To address this, we performed co-precipitation experiments using a monoclonal antibody directed against the FasL N-terminus for subsequent protein detection of full length FasL and NTFs/ICDs in Western blots. We demonstrate that members of the sorting nexin (SNX) family bind full length FasL and its N-terminal fragments whereas members of the Pombe Cdc15 homology (PCH) protein family bind full length FasL, but fail to associate with processed FasL. Thus, we provide first evidence that full length FasL and FasL fragments display selectivity regarding their association with intracellular binding partners. The differential binding most likely governs the fate and function of the intracellular FasL fragments.
Experimental cell research.Exp Cell Res.2014 Jan 15;320(2):290-301. doi: 10.1016/j.yexcr.2013.11.016. Epub 2013 Nov 26.
Fas ligand (FasL) is a death factor of the tumor necrosis factor superfamily. Like other members of this family of type II transmembrane proteins, FasL is subject to ectodomain shedding by a disintegrin and metalloproteinases (ADAMs) liberating soluble FasL and leaving membrane-integral N-terminal f
PMID 24291222

Chemical Synthesis of Insulin Analogs through a Novel Precursor.

Zaykov AN, Mayer JP, Gelfanov VM, Dimarchi RD.Author information Indiana University , Department of Chemistry, Bloomington, Indiana 47405, United States of America.AbstractInsulin remains a challenging synthetic target due in large part to its two-chain, disulfide-constrained structure. Biomimetic single chain precursors inspired by proinsulin that utilize short peptides to join the A and B chains can dramatically enhance folding efficiency. Systematic chemical analysis of insulin precursors using an optimized synthetic protocol identified a 49 amino acid peptide named DesDi, which folds with high efficiency by virtue of an optimized structure and could be proteolytically converted to bioactive two-chain insulin. In subsequent applications, we observed that the folding of the DesDi precursor was highly tolerant to amino acid substitution at various insulin residues. The versatility of DesDi as a synthetic insulin precursor was demonstrated through the preparation of several alanine mutants (A10, A16, A18, B12, B15), as well as ValA16, an analog that was unattainable in prior reports. In vitro bioanalysis highlighted the importance of the native, hydrophobic residues at A16 and B15 as part of the core structure of the hormone and revealed the significance of the A18 residue to receptor selectivity. We propose that the DesDi precursor is a versatile synthetic intermediate for the preparation of diverse insulin analogs. It should enable a more comprehensive analysis of function to insulin structure than might not be otherwise possible through conventional approaches.
ACS chemical biology.ACS Chem Biol.2014 Jan 2. [Epub ahead of print]
Insulin remains a challenging synthetic target due in large part to its two-chain, disulfide-constrained structure. Biomimetic single chain precursors inspired by proinsulin that utilize short peptides to join the A and B chains can dramatically enhance folding efficiency. Systematic chemical analys
PMID 24328449

T lymphocytes export proteasomes by way of microparticles: a possible mechanism for generation of extracellular proteasomes.

Bochmann I, Ebstein F, Lehmann A, Wohlschlaeger J, Sixt SU, Kloetzel PM, Dahlmann B.Author information Institut für Biochemie, Charité-Universitätsmedizin Berlin, Berlin, Germany.AbstractThe 20S proteasome is almost exclusively localized within cells. High levels of extracellular proteasomes are also found circulating in the blood plasma of patients suffering from a variety of inflammatory, autoimmune and neoplastic diseases. However, the origin of these proteasomes remained enigmatic. Since the proteome of microparticles, small membrane enclosed vesicles released from cells, was shown to contain proteasomal subunits, we studied whether intact proteasomes are actively released into the extracellular space. Using human primary T lymphocytes stimulated with CaCl2 and the calcium ionophore A23187 to induce membrane blebbing we demonstrate that microparticles contain proteolytically active 20S proteasomes as well as the proteasome activator PA28 and subunits of the 19S proteasome regulator. Furthermore, our experiments reveal that incubation of in vitro generated T lymphocyte-microparticles with sphingomyelinase results in the hydrolysis of the microparticle membranes and subsequent release of proteasomes from the vesicles. Thus, we here show for the first time that functional proteasomes can be exported from activated immune cells by way of microparticles, the dissolution of which may finally lead to the generation of extracellular proteasomes.
Journal of cellular and molecular medicine.J Cell Mol Med.2014 Jan;18(1):59-68. doi: 10.1111/jcmm.12160. Epub 2013 Oct 31.
The 20S proteasome is almost exclusively localized within cells. High levels of extracellular proteasomes are also found circulating in the blood plasma of patients suffering from a variety of inflammatory, autoimmune and neoplastic diseases. However, the origin of these proteasomes remained enigmat
PMID 24304442