title: Targeting the ubiquitin pathway for cancer treatment.
abstract: Proteasome-mediated degradation is a common mechanism by which cells renew their intracellular proteins and maintain protein homeostasis. In this process, the E3 ubiquitin ligases are responsible for targeting specific substrates (proteins) for ubiquitin-mediated degradation. However, in cancer cells, the stability and the balance between oncoproteins and tumor suppressor proteins are disturbed in part due to deregulated proteasome-mediated degradation. This ultimately leads to either stabilization of oncoprotein(s) or increased degradation of tumor suppressor(s), contributing to tumorigenesis and cancer progression. Therefore, E3 ubiquitin ligases including the SCF types of ubiquitin ligases have recently evolved as promising therapeutic targets for the development of novel anti-cancer drugs. In this review, we highlighted the critical components along the ubiquitin pathway including E1, E2, various E3 enzymes and DUBs that could serve as potential drug targets and also described the available bioactive compounds that target the ubiquitin pathway to control various cancers.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Shavali
authors.initials: S
authors.lastname: Shaik
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Xiangpeng
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China.
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China. Electronic address: zhiweichina@126.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: wwei2@bidmc.harvard.edu.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction; D025801:Ubiquitin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D044763:Ubiquitin-Conjugating Enzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000502:physiology; D064570:Ubiquitin-Specific Proteases / Q000037:antagonists & inhibitors / Q000502:physiology; D054875:Ubiquitination / Q000502:physiology
chemical_list: D061988:Proteasome Inhibitors; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D064570:Ubiquitin-Specific Proteases; D046988:Proteasome Endopeptidase Complex; D044764:Ubiquitin-Activating Enzymes
keywords: Cancer; Deubiquitinating enzyme; Drug targets; SCF; Ubiquitin ligase