Interplay between the ubiquitin-proteasome system and autophagy in proteinopathies

Qingwen Zheng, Jie Li, Xuejun Wang

Research output: Contribution to journalReview article

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)127-142
Number of pages16
JournalInternational Journal of Physiology, Pathophysiology and Pharmacology
Volume1
Issue number2
StatePublished - Dec 1 2009

Fingerprint

Autophagy
Proteasome Endopeptidase Complex
Ubiquitin
Proteins
Pharmacology
Poisons
Starvation
Quality Control
Organelles
Proteolysis
Life Style
Cytoplasm
Animal Models

Keywords

  • Autophagy
  • FoxO3
  • HADC6
  • Proteinopathy
  • Ubiquitin proteasome system
  • p62

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Physiology
  • Physiology (medical)

Cite this

Interplay between the ubiquitin-proteasome system and autophagy in proteinopathies. / Zheng, Qingwen; Li, Jie; Wang, Xuejun.

In: International Journal of Physiology, Pathophysiology and Pharmacology, Vol. 1, No. 2, 01.12.2009, p. 127-142.

Research output: Contribution to journalReview article

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