Proteolysis Ubiquitin proteasom

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

WojciK, C., Yano, M., and DeMartino, G. N. RNA interference of valosin-containing protein (VCP/ p97) reveals multiple cellular roles linked to ubiquitin/ proteasome-dependent proteolysis. J Cell Sd 2004, 117, 281-92. 

Role of Ubiquitin-Proteasome-Mediated Proteolysis in the Cell Cycle 735... 

Ubiquitin-proteasome-mediated proteolysis plays a critical role in many physiological processes including cell cycle and development. In the nervous system, proteolysis plays a role in the formation of synaptic connections during development as well as in alteration of synaptic strength (synaptic plasticity) that occurs during learning and memory. The role of proteolysis in cell cycle and synaptic plasticity will be considered in detail below. 

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. 

Given that proteolysis by the ubiquitin-proteasome pathway plays a critical role in the control of cell proliferation, it is expected to have a role in cancer, which is basically uncontrolled cell proliferation. Many substrates, UBCs, ubiquitin ligases, DUBs, and the proteasome are all implicated in cancer pathogenesis (Table 7). 

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. 

Ubiquitin interacts avidly but not covalently with ABP and such complexes can be isolated from AD brain extracts (276). Ubiquitin and APP colocalize to endosome-lysosomes implicated in APP proteolysis (277). A clear link between defective APP processing and the ubiquitin-proteasome system was demonstrated by Chen et al. 

Dantuma NP, Lindsten K, Glas R, Jellne M, and Masucci MG (2000b) Short-lived green fluorescent proteins for quantification of ubiquitin/proteasome-dependent proteolysis in living cells. Nat. Biotech. 18 538-543. 

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