Role of the Ubiquitin-Proteasome System

Ye Y. The role of the ubiquitin-proteasome system in ER quality control. Essays Biochem. 2005 41 99-112. 

Table 8 Role of the ubiquitin-proteasome pathway in nonnervous system diseases...

In concordance with the central role of ubiquitin modification in multiple cellular functions perturbations of this system are associated with a variety of diseases. Defects in the control of cell cycle regulators by the ubiquitin proteasome system are connected to cancer progression and many E3 ligases were originally identified as oncogenes. 

Although ubiquitin was used as a marker for brain pathology, no physiological or pathological role for ubiquitin in the nervous system was found until about a decade ago. The first discovery of ubiquitin—proteasome-mediated degradation of a physiologically relevant substrate in the nervous system was that of R subunits of PKA. Since then several substrates of the ubiquitin—proteasome pathway in the nervous system have been identified (Table 6). 

The intracellular deposition of ABP as the first pathogenic event prior to the appearance of tau pathology in AD (272) is an indirect evidence of ABP aggregation and incapacity of the ubiquitin-proteasome-chaperone system to repair the distorted metabolism of APP-ABP leading to neurodegeneration. A similar phenomenon with aggregation of conformation-abnormal peptides probably plays a key role in many other neurodegenerative disorders. 

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