Intramembrane proteolysis by γ-secretases plays major roles in disease pathology and cellular signalling, yet the dynamics of these enzyme complexes and how they recognize substrates remains poorly understood. New work in The EMBO Journal utilizes photoaffinity crosslinking to map APP interactions to different γ-secretase subunits, suggesting a succession of recruitment and engagement steps tha...

Ubiquitin, an evolutionary highly conserved protein, is known to be involved in selective proteolysis in the cytoplasm. Here we show that ubiquitin-protein conjugates are also found in the yeast vacuole. Mutants defective in the major vacuolar endopeptidases, proteinase yscA and yscB, lead to accumulation of ubiquitin-protein conjugates in this cellular organelle.

Intramembrane proteolysis by c-secretases plays major roles in disease pathology and cellular signalling, yet the dynamics of these enzyme complexes and how they recognize substrates remains poorly understood. New work in The EMBO Journal utilizes photo-affinity cross-linking to map APP interactions to different c-secretase subunits, suggesting a succession of recruitment and engagement steps t...

Perfluorinated compounds (PFCs) such as perfluorooctanesulfonate (PFOS) are stable chemicals that accumulate in biological matrix. Toxicity of these compounds including immunotoxicity has been demonstrated in experimental models and wildlife. Although limited number of studies examined the effects of PFOS on human lymphocytes but so far no research has investigated the complete mechanisms of PF...

Each step of the seed-to-seed cycle of plant development including seed germination is characterized by a specific set of proteins. The continual renewal and/or replacement of these biomolecules are crucial for optimal plant adaptation. As proteins are the main effectors inside the cells, their levels need to be tightly regulated. This is partially achieved by specific proteolytic pathways via ...

Overexpression of cyclin E in breast tumors is associated with a poor response to tamoxifen therapy, greater genomic instability, more aggressive behavior, and a poor clinical prognosis. These tumors also express low molecular weight isoforms of cyclin E that are associated with higher kinase activity and increased metastatic potential. In the current study, we show that cyclin E overexpression...

Disruption of neuronal Ca homeostasis plays a well-established role in cell death in a number of neurodegenerative disorders. Recent evidence suggests that proteolysis of the type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1), a Ca 2+ release channel on the endoplasmic reticulum, generates a dysregulated channel, which may contribute to aberrant Ca signaling and neurodegeneration in disease...

Previous work has suggested that intracellular proteolysis may play a role in lymphocyte stimulation. An inhibitor of proteolysis, epsilon amino caproic acid (EACA) was studied for its effect on the lymphocyte response to phytohemagglutinin (PHA). EACA was found to inhibit several parameters of lymphocyte stimulation (e.g. DNA, RNA, and protein synthesis as well as alterations in morphology) Th...

Ubiquitination, a highly versatile process of protein homeostasis, participates in the degradation vast majority cellular proteins. In addition to proteolytic function, ubiquitination can also conduce modulate processes independent proteolysis, such as signal transduction, trafficking, DNA repair and so on. Apoptosis modulates cell quantity via orderly removing damaged cells effectively plays f...