Ubiquitin, proteolysis pathway mediation

Many diseases have been linked to components of the ubiquitin-proteasome pathway. These diseases affect several tissues and systems of the body. Major diseases connected to ubiquitin—proteasome-mediated proteolysis are different types of cancer and numerous diseases and disorders of the brain. 

Alterations in the ubiquitin-proteasome pathway have been connected to several neurodegenerative diseases (Table 9). In some instances, mutations in specific genes have been linked to the etiology of the disease. Although the perturbations in ubiquitin-proteasome-mediated proteolysis lead to pleiotropic effects on neurons including cell death or degeneration, one of the early effects is believed to be synaptic malfunction. 

Fig. 2.16 Regu lation and proteolysis of the transcription factor NFkB. The Ubiquitin-protea-some pathway is involved in the regulation of NFkB in two ways. The 50 kDa subunit of NFkB is formed from a 105 kDa precursor via ubiquitin mediated proteolysis. In the cytosol NFkB is heterodimeric and inactive, bound to the inhibitor protein IkB.

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