The ubiquitin-proteasome pathway.
Regulating protein stability and turnover is a key task in the cell. Besides lysosomes, ubiquitin-mediated proteasomal degradation comprises the major proteolytic pathway in eukaryotes. Proteins destined for degradation by the proteasome are conjugated by a 'tag', a ubiquitin chain to a lysine, through an extensively regulated enzymatic cascade. 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. 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. 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. Therefore, dissecting the ubiquitin-proteasome pathway and identifying proteins involved in conjunction with the signals required for specific degradation of certain substrates, would help in developing novel therapeutic approaches to treat diseases where the ubiquitin-proteasome pathway is impaired.
Roos-Mattjus
Pia
P
Department of Biology, Abo Akademi University, Turku Centre for Biotechnology, Abo Akademi University & University of Turku, Turku, Finland.
Sistonen
Lea
L
D003546:Cysteine Endopeptidases / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009097:Multienzyme Complexes; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex