Ubiquitin proteasome proteolysis

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

The 26S proteasome also degrades non-ubiquitylated proteins [71]. The short-lived enzyme ornithine decarboxylase (ODC) and the cell-cycle regulator p21Cip provide well documented examples of ubiquitin-independent proteolysis by the 26S en-... 

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. 

Protein aggregation is a common feature of all of the chronic human neurode-generative disorders. The intraneuronal inclusions in many of these diseases contain deposits of ubiquitylated proteins, indicating that perturbations of ubiquitin-dependent proteolysis may occur. The neuropathological hallmarks of AD are intraneuronal NFTs composed of hyperphosphorylated protein tau and extracellular amyloid plaques (12,23,24,191,207). Most of the ubiquitylated, hyperphosphorylated tau protein in NETs is monoubiquitylated, with the remainder polyubiquitylated, as the substrate of the 26S proteasome (258). The protein deposits in NET, neuritic plaques, and neuropil threads in the cerebral cortex of AD patients and those with... 

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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