search for




 

Regulation of Protein Degradation by Proteasomes in Cancer
Journal of Cancer Prevention 2018;23:153-61
Published online December 30, 2018
© 2018 Korean Society of Cancer Prevention.

Ho Hee Jang

Department of Biochemistry, College of Medicine, Gachon University, Incheon, Korea
Correspondence to: Ho Hee Jang
Department of Biochemistry, College of Medicine, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Korea
Tel: +82-32-899-6317, Fax: +82-32-899-6318, E-mail: hhjang@gachon.ac.kr
ORCID: Ho Hee Jang, https://orcid.org/0000-0003-0314-8230
Received December 7, 2018; Revised December 15, 2018; Accepted December 18, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Imbalance of protein homeostasis (proteostasis) is known to cause cellular malfunction, cell death, and diseases. Elaborate regulation of protein synthesis and degradation is one of the important processes in maintaining normal cellular functions. Protein degradation pathways in eukaryotes are largely divided into proteasome-mediated degradation and lysosome-mediated degradation. Proteasome is a multisubunit complex that selectively degrades 80% to 90% of cellular proteins. Proteasome-mediated degradation can be divided into 26S proteasome (20S proteasome 竊 19S regulatory particle) and free 20S proteasome degradation. In 1980, it was discovered that during ubiquitination process, wherein ubiquitin binds to a substrate protein in an ATP-dependent manner, ubiquitin acts as a degrading signal to degrade the substrate protein via proteasome. Conversely, 20S proteasome degrades the substrate protein without using ATP or ubiquitin because it recognizes the oxidized and structurally modified hydrophobic patch of the substrate protein. To date, most studies have focused on protein degradation via 26S proteasome. This review describes the 26S/20S proteasomal pathway of protein degradation and discusses the potential of proteasome as therapeutic targets for cancer treatment as well as against diseases caused by abnormalities in the proteolytic system.
Keywords : Proteasome, Ubiquitination, Oxidative stress, Protein degradation, Cancer


December 2018, 23 (4)
Full Text(PDF) Free

Social Network Service

Cited By Articles
  • CrossRef (0)

Author ORCID Information

Services