Ubiquitin, a central component of selective cytoplasmic proteolysis, is linked to proteins residing at the locus of non-selective proteolysis, the vacuole

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.

Attempt on Magnification of the Mechanism of Enzyme Catalyzed Reaction through Bio-geometric Model for the Five Points Circle in the Triangular Form of Lineweaver-Burk Plot

oai:sciengtexopen.org:article/120The bio-geometrical model is dealing with correlation between the “five events for enzyme catalyzed reaction” and “triple point event serving groups on the circle” in triangle obtained for the graphical presentation of the double reciprocal for magnification of the mechanism of enzyme catalyzed reaction. This model is based on the nine point circle in triangle of the double reciprocal plot. The five significant points (B, D, E, F and G) resulted for the circle with x – and y – coordinates. The present attempt is considering interactions among enzymes and substrates for the successful release of product through each and every point on the circle in triangle. The controlling role of the point, “O”, center of circle in each and every event of the biochemical reaction is obligatory.  The model is allotting specific role for the significant events in the biochemical reaction catalyzed by the enzymes. The enzymatic catalysis is supposed to be completed through five events, which may be named as, “Bio-geometrical events of enzyme catalyzed reaction”. These five events for enzyme catalyzed reaction include: (1) Initial event of enzymatic interaction with the substrates; (2) Event of the first transition state for the formation of “enzyme-substrate” complex; (3) Event of the second transition state for the formation of “enzyme-product” complex; (4) Event of release of the product and relieve enzyme and (5) The event of directing the enzyme to continue the reaction. The model utilizes the “triple point serving group on the circle” for the success of each and every event in the biochemical reaction. Thus, there is involvement of the three points including the point “O” for each event in the enzyme catalyzed reaction. The group of points serving for carrying out the event may be classified into five conic sections like: B-O-E; E-O-G; G-O-D; D-O-F and F-O-B. The bio-geometrical model is correlation between the “five events for enzyme catalyzed reaction” and “triple point event serving groups on the circle” in a triangle of the double reciprocal plot

Ubiquitination of Aquaporin-2 in the Kidney

Ubiquitination is known to be important for endocytosis and lysosomal degradation of aquaporin-2 (AQP2). Ubiquitin (Ub) is covalently attached to the lysine residue of the substrate proteins and activation and attachment of Ub to a target protein is mediated by the action of three enzymes (i.e., E1, E2, and E3). In particular, E3 Ub-protein ligases are known to have substrate specificity. This minireview will discuss the ubiquitination of AQP2 and identification of potential E3 Ub-protein ligases for 1-deamino-8-D-arginine vasopressin (dDAVP)-dependent AQP2 regulation

T Cell-Mediated Modulation of Mast Cell Function: Heterotypic Adhesion-Induced Stimulatory or Inhibitory Effects

Close physical proximity between mast cells and T cells has been demonstrated in several T cell mediated inflammatory processes such as rheumatoid arthritis and sarcoidosis. However, the way by which mast cells are activated in these T cell-mediated immune responses has not been fully elucidated. We have identified and characterized a novel mast cell activation pathway initiated by physical contact with activated T cells, and showed that this pathway is associated with degranulation and cytokine release. The signaling events associated with this pathway of mast cell activation have also been elucidated confirming the activation of the Ras mitogen-activated protein kinase systems. More recently, we hypothesized and demonstrated that mast cells may also be activated by microparticles released from activated T cells that are considered as miniature version of a cell. By extension, microparticles might affect the activity of mast cells, which are usually not in direct contact with T cells at the inflammatory site. Recent works have also focused on the effects of regulatory T cells (Treg) on mast cells. These reports highlighted the importance of the cytokines IL-2 and IL-9, produced by mast cells and T cells, respectively, in obtaining optimal immune suppression. Finally, physical contact, associated by OX40–OX40L engagement has been found to underlie the down-regulatory effects exerted by Treg on mast cell function

Learning through designing robots in the framework of school graduation projects in Israel

This paper describes how students in Israel develop robots and participate in the Trinity College Fire-Fighting Home Robot Contests in the curricular framework of the school graduation project. We consider robotics projects developed in the Mevohot E’ron High School in 1999-2002 and specify the interdisciplinary activities of the teams designing fire-fighting robots. Our research focuses on the assessment of learning while working in the teams. The proposed approach is based on the triangulation of ethnographic observations of teamwork, examination of learning achievements, and analysis of robot contest surveys. Results of the study gave a picture of students’ behaviours at different stages of the design process, as needed for the individual assessment. As found, each of the students had made progress in a number of subjects and took a significant part in making the robot

Discovery of cellular regulation by protein degradation

What follows is a story of some of the lab’s adventures mentioned above, including the inventions of new biochemical and genetic methods. This account stems, in part, from previous descriptions of the early history of the Ub field (31,32). Another antecedent is an interview I gave to Dr. Istvan Hargittai, a distinguished Hungarian chemist. It describes my life and science, including the early years in Moscow, the 1977 escape from the former Soviet Union, the essentially accidental hiring of me by MIT, and the work that ensued (33). The narrative below borrows from these sources, and mentions our more recent contributions as well

Generation and physiological roles of linear ubiquitin chains

Ubiquitination now ranks with phosphorylation as one of the best-studied post-translational modifications of proteins with broad regulatory roles across all of biology. Ubiquitination usually involves the addition of ubiquitin chains to target protein molecules, and these may be of eight different types, seven of which involve the linkage of one of the seven internal lysine (K) residues in one ubiquitin molecule to the carboxy-terminal diglycine of the next. In the eighth, the so-called linear ubiquitin chains, the linkage is between the amino-terminal amino group of methionine on a ubiquitin that is conjugated with a target protein and the carboxy-terminal carboxy group of the incoming ubiquitin. Physiological roles are well established for K48-linked chains, which are essential for signaling proteasomal degradation of proteins, and for K63-linked chains, which play a part in recruitment of DNA repair enzymes, cell signaling and endocytosis. We focus here on linear ubiquitin chains, how they are assembled, and how three different avenues of research have indicated physiological roles for linear ubiquitination in innate and adaptive immunity and suppression of inflammation