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. 2009 May 8;1(2):127-42.

Interplay between the ubiquitin-proteasome system and autophagy in proteinopathies

Qingwen Zheng  1 , Jie Li, Xuejun Wang
Affiliations

Interplay between the ubiquitin-proteasome system and autophagy in proteinopathies

Qingwen Zheng et al. Int J Physiol Pathophysiol Pharmacol. .

Abstract

Proteinopathies are a family of human disease caused by toxic aggregation-prone proteins and featured by the presence of protein aggregates in the affected cells. The ubiquitin-proteasome system (UPS) and autophagy are two major intracellular protein degradation pathways. The UPS mediates the targeted degradation of most normal proteins after performing their normal functions as well as the removal of abnormal, soluble proteins. Autophagy is mainly responsible for degradation of defective organelles and the bulk degradation of cytoplasm during starvation. The collaboration between the UPS and autophagy appears to be essential to protein quality control in the cell. UPS proteolytic function often becomes inadequate in proteinopathies which may lead to activation of autophagy, striving to remove abnormal proteins especially the aggregated forms. HADC6, p62, and FoxO3 may play an important role in mobilizing this proteolytic consortium. Benign measures to enhance proteasome function are currently lacking; however, enhancement of autophagy via pharmacological intervention and/or lifestyle change has shown great promise in alleviating bona fide proteinopathies in the cell and animal models. These pharmacological interventions are expected to be applied clinically to treat human proteinopathies in the near future.

Keywords: FoxO3; HADC6; Ubiquitin proteasome system; autophagy; p62; proteinopathy.

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Figures

Figure 1
Figure 1
An illustration of the ubiquitin-proteasome system for intracellular protein degradation.
Figure 2
Figure 2
A thematic illustration of the interplay between the ubiquitin-proteasome system and autophagy in proteinopathy
See this image and copyright information in PMC

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