Proteasome ubiquitinated

Proteasome inhibitors have been instrumental in identifying numerous protein substrates and in elucidating the importance of the proteasome/ubiquitin pathway in many biological processes. Initially, non-specific cell-penetrating peptide aldehydes were used for this purpose. More recently, it became possible to synthesize compounds with increased potency and selectivity (Adams et al. 1998 Elofsson et al. 1999). Furthermore, based on the crystal structure of the yeast and bovine liver CP (Groll et al. 1997 Unno et al. 2002), molecular modeling can now be used to engineer improved inhibitors. 

Altar CA, et al. 2005. Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial... 

Altar CA, Jurata LW, Charles V, Lemire A, Liu P, et al. 2005. Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts. Biol Psychiatry 58 85-96. 

The covalent attachment of multiple ubiquitin molecules to one or more lysines within a protein provides a well-established means of targeting the protein for destruction by the proteasome. Ubiquitination involves a set of enzymes that sequentially activate ubiquitin (El enzyme), conjugate it to the substrate (E2 or E3 enzyme), and elongate the multi-ubiquitin chain (E3 enzyme) (Hershko and CiECHANOVER 1998). Although El is a universal enzyme, E2 and particularly E3 enzymes usually have specificity for only one or a few degradation substrates. 

Vol. 268 ZwickI, Peter Baumeister, Wolfgang (Eds.) The Proteasome-Ubiquitin Protein Degradation Pathway. 2002, X, 213 pp. ISBN 3-540-43096-2... 

Emerging evidence suggests that dysfunction of the ubiquitin-proteasome system may be part of the pathophysiology of sporadic Parkinson s disease, especially... 

In addition to protein proteolysis during mitosis, ubiquitin-mediated protein degradation ( ubiquitin/ proteasome) is also required at the G1 to S transition... 

The human genome contains more than 90 different DUBs. Besides cleaving ubiquitin from distinct substrates, DUBs are also responsible for the recycling of free ubiquitin from ubiquitin chains and processing of ubiquitin- or ubiquitin like precursor proteins. Certain DUBs are also associated with the proteasome in order to detach ubiquitin chains before proteolysis. 

Transforming Growth Factor-Beta Ubiquitin/Proteasome... 

F-adjacent Transcript-10 (FAT 10) is composed of two ubiquitin-like domains and capable to mark conjugated proteins for proteasomal degradation independent of ubiquitin. FAT10 is inducible by IFN-y and TNF and induces apoptosis when over expressed. 

Ubiquitin tags proteins for protein degradation. The ubiquitination requires three different enzymatic activities, a ubiquitin-activating enzyme (El), a ubiquitin-conjugating enzyme (E2 or Ubc) and a ubiquitin ligase (E3). The action of all three enzymes leads to the establishment of a poly-ubiquitin chain on target proteins which are then recognized and proteolyzed by the 26S proteasome. 

Protein modification by the covalent attachment of ubiquitin chains serves as a signal to mark proteins for the degradation by a multicatalytic proteinase complex called the proteasome. Thus the ubiquitin proteasome system (UPS) controls the stability of proteins in a... 

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