Ubiquitin-Proteasome Pathway-enzyme

The Ubiquitin Proteasome Pathway (UPP) is the principal mechanism for protein catabolism in the mammalian cytosol and nucleus. The highly regulated UPP affects a wide variety of cellular processes and substrates and defects in the system can result in the pathogenesis of several important human diseases. The UPP is central to the regulation of almost all cellular processes including:

The Ubiquitin Proteasome Pathway (UPP) is the principal mechanism for protein catabolism in the mammalian cytosol and nucleus

The ubiquitin proteasome pathway, is required for the targeted degradation of most shortlived proteins in the eukaryotic cell. Targets include cell cycle regulatory proteins, whose timely destruction is vital for controlled cell division, as well as proteins unable to fold properly within the endoplasmic reticulum. Ubiquitin modification is an ATP-dependent process carried out by three classes of enzymes. Depending on the number of ubiquitin moieties and the linkages made, ubiquitin also plays an important role in DNA repair, protein sorting and virus budding. Polyubiquitin chains are also indicated in diverse cellular processes including DNA damage response, mitochondrial maintenance and mitophagy, lysosomal degradation, T Cell Receptor signaling, and NF-κB signaling. Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action.

The ubiquitylated proteins are subsequently targeted for degradation by the 26S proteasome, the major proteolytic machinery for ubiquitylated proteins in the cell. Ubiquitylation can be considered as another covalent post-translational modification and signal, comparable to acetylation, glycosylation, methylation, and phosphorylation. However, ubiquitylation has multiple roles in addition to targeting proteins for degradation. Unregulated degradation of proteins, or abnormally stable proteins, interfere with several regulatory pathways, and the ubiquitin-proteasome pathway is affected in a number of diseases, such as neurodegenerative diseases, cellular atrophies and malignancies.

Ubiquitin-Activating E1 Enzyme list
CENPU CNPY2 CUEDC2
HGS RNF11 RPS27A
Deubiquitinase list
JOSD1 OTUB1 OTUB2
UBXN6 UCHL1 UCHL3
UCHL5 USP5 USP7
USP8 USP10 USP18
USP21 USP22 USP29
USP30 USP32 USP33
USP37 USP38 USP46
USP49    
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