Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

A-Proteasome

Proteasomal inhibition represents a novel strategy in cancer treatment and the small molecule Bortezomid (PS-341, Velcade ) has been approved for the treatment of refractory and relapsed multiple myeloma, a proliferative disease of plasma cells. Bortezomid inhibits an active site in a proteasome subunit and remarkably shows selective cytotoxicity to cancer cells. Although the underlying mechanisms are not completely understood bortezomid apparently induces a cell stress response in these tumor cells followed by caspase-dependent apoptosis. Whether bortezomid is beneficial for the treatment of other proliferative disease is currently being tested in clinical trials. [Pg.1266]

In addition to the RC there are two protein complexes, REGajS and REGy, and a single polypeptide chain, PA200, that bind the 20S proteasome and stimulate peptide hydrolysis but not protein degradation. Like the RG, proteasome activators bind the ends of the 20 S proteasome and, importantly, they can form mixed or hybrid 26S proteasomes in which one end of the 20S proteasome is associated with a 19S RC and the other is bound to a proteasome activator [147-150]. This latter property raises the possibility that proteasome activators serve to localize the 26S proteasome within eukaryotic cells. [Pg.236]

Santamaria, P. G., Finley, D., Ballesta, j. P., and Remacha, M. Rpn6p, a proteasome subunit from Saccharomyces cerevisiae, is essential for the assembly and activity of the 26S proteasome. J Biol Chem 2003,... [Pg.245]

Belactosin A - proteasome inhibitor, antiproliferative and antitumor activities Belactosin B - inactive member... [Pg.34]

Site-directed mutagenesis and the crystal structure analysis of a proteasome-inhibitor complex identified the amino-terminal threonine (Thrl) of Thermoplasma P subunits as both, the catalytic nucleophile and the primary proton acceptor (Seemiiller et al. 1995 Lowe et al. 1995). [Pg.69]

Ohba, M. A 70-kDa heat shock cognate protein suppresses the defects caused by a proteasome mutation in Saccharomyces cerevisiae. FEBS Lett. 351 263-6.1994. [Pg.135]

Mayer TU, Braun T, Jentsch, S (1998) Role of the proteasome in membrane extraction of a short-lived ER-transmembrane protein. EMBO ] 17 3251-3257 McCracken AA, Brodsky JL (1996) Assembly of ER-associated protein degradation in vitro dependence on cytosol, calnexin, and ATP. J Cell Biol 132 291-298 McDonald HB, Byers B (1997) A proteasome cap subunit required for spindle pole body duplication in yeast. J Cell Biol 137 539-553 McGee TP, Cheng HH, Kumagai H, Omura S, Simoni RD (1996) Degradation of 3-hydroxy-3-methylg utaryl-CoA reductase in endoplasmic reticulum membranes is accelerated as a result of increased susceptibility to proteolysis. J Biol Chem 271 25630-25638... [Pg.154]

Blocking of Protein Degradation of HaloTag-CL1 by a Proteasome Inhibitor MG132... [Pg.128]

Zhang DD, Lo SC, Sun Z, Habib GM, Lieberman MW, Hannink M. 2005. Ubiquitination of Keapl, a BTB-Kelch substrate adaptor protein for Cul3, targets Keapl for degradation by a proteasome-independent pathway. J Biol Chem 280 30091-30099. [Pg.426]

Different hypotheses have been raised to explain these purported beneficial effects. Ono et al. have shown that the neuroprotective effects of various polyphenols (e.g., myricetin, morin, and, to a lesser extent, quercetin) may be due to their ability to inhibit amyloid fibrils and to destabilize fibrilized forms of Ap,20 suggesting that they could be considered as new therapeutic agents for the treatment of AP-associated diseases.21 Resveratrol, a red-wine polyphenol, has been proposed to promote the intracellular degradation of Ap by a proteasome-dependent and secretase-independent activity.22 Based on these findings, we compared the effects of polyphenols found in teas and red wine, using the model of AP-induced toxicity in rat hippocampal primary cell cultures. [Pg.108]

Next let us show how one can compute the proteasome output if the transport rates are given. In our model we assume that the proteasome has a single channel for the entry of the substrate with two cleavage centers present at the same distance from the ends, yielding in a symmetric structure as confirmed by experimental studies of its structure. In reality a proteasome has six cleavage sites spatially distributed around its central channel. However, due to the geometry of its locations, we believe that a translocated protein meets only two of them. Whether the strand is indeed transported or cleaved at a particular position is a stochastic process with certain probabilities (see Fig. 14.5). [Pg.381]

These mechanistic findings supported the exploration of the therapeutic potential of proteasome inhibitors in oncology, with the first clinical trials involving a proteasome inhibitor (bortezomib) commencing about ten years ago. Lessons learned from bench to bedside during this time period have recently been reviewed.19... [Pg.357]

Associated Protein synthesis. See Werner, E.D., Brodsky, J.L., and McCracken, A.A., Proteasome-Degradation dependent endoplasmic reticulum-associated protein degradation an... [Pg.97]

Recent pursuit of marine microbial sources led to the isolation of salinosporamide A (83). It is a P-lactone produced by the marine bacteria Salinispora tropica and is a proteasome inhibitor (86). Mechaiustically, it works by specific covalent modification of the target. This compound has entered human cliiucal development for treatment of multiple myeloma (87-89). [Pg.1469]

Proteins in the human body have a limited lifetime. They are earmarked for degradation with a marker ubiquitin and hydrolysed by proteasomes. Though this is a natural and necessary sequence of events it can get out of hand and proteasome inhibitors could provide treatments for heart diseases, asthma, and arthritis. Lactacystin 112 is a proteasome inhibitor from a soil micro-organism. [Pg.734]

A number of inhibitors of various tyrosine kinase enzymes are important new cancer drugs sunitinib (Sutent) is used for the treatment of certain kidney and GI cancers imatinib (Glivec) for chronic myeloid leukemia and GI tumours, and lapatinib (Tykerb/Tykerv) for breast and lung cancers. Bortezomib (Velcade), a proteasome inhibitor is used to treat multiple myeloma and is notable for being a boronic acid. [Pg.662]


See other pages where A-Proteasome is mentioned: [Pg.1263]    [Pg.360]    [Pg.205]    [Pg.206]    [Pg.233]    [Pg.241]    [Pg.291]    [Pg.313]    [Pg.345]    [Pg.715]    [Pg.721]    [Pg.721]    [Pg.722]    [Pg.733]    [Pg.23]    [Pg.199]    [Pg.123]    [Pg.142]    [Pg.128]    [Pg.245]    [Pg.30]    [Pg.150]    [Pg.446]    [Pg.1263]    [Pg.185]    [Pg.282]    [Pg.464]    [Pg.133]    [Pg.316]    [Pg.2482]    [Pg.46]    [Pg.144]    [Pg.193]   
See also in sourсe #XX -- [ Pg.446 ]




SEARCH



HslVU Peptidase as a Model for the Eukaryotic 26S Proteasome

Proteasome

The Proteasome as a Drug Target

The Ubiquitin-Proteasome System as a Target for Drug Development

© 2024 chempedia.info