Function
Ubiquitin (UBB) is found in almost all cells. It binds to proteins tagging them for destruction in the proteasome. UBB is activated by the UBB-activating enzymes E1, E2 and E3. UBB+1 is a frameshifted mutant of UBB observed in several diseases. A dimer of UBB (DiUBB) is formed by linkage of K48 to the C-terminus of a second UBB molecule. At least 4 UBB molecules are needed to tag a protein for the proteasome[1]. Human ubiquitin interactions with ubiquitin-conjugating enzyme E2 (3k9p). For details see
Professors Ciechanover, Hershko and Rose received the Nobel Prize in 2004 for their discovery of the process by which ubiquitin mediates protein proteolysis[2].
Additional Resources
See also:
Disease
The UBB-proteasome system deregulation has been implicated in the pathogenesis of many neurodegenerative disorders like Alzheimer's disease, Parkinson disease, Huntington disease, Prion-like lethal disorders and in genetic diseases like cystic fibrosis, angelman's syndrome, Liddle syndrome and many cancers[3].
- ↑ Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425-79. PMID:9759494 doi:https://dx.doi.org/10.1146/annurev.biochem.67.1.425
- ↑ Neefjes J, Groothuis TA, Dantuma NP. [The 2004 Nobel Prize in Chemistry for the discovery of ubiquitin-mediated protein degradation]. Ned Tijdschr Geneeskd. 2004 Dec 25;148(52):2579-82 PMID:15646859
- ↑ Paul S. Dysfunction of the ubiquitin-proteasome system in multiple disease conditions: therapeutic approaches. Bioessays. 2008 Nov;30(11-12):1172-84. doi: 10.1002/bies.20852. PMID:18937370 doi:https://dx.doi.org/10.1002/bies.20852