title: Targeting ubiquitination for cancer therapies.
abstract: Ubiquitination, the structured degradation and turnover of cellular proteins, is regulated by the ubiquitin-proteasome system (UPS). Most proteins that are critical for cellular regulations and functions are targets of the process. Ubiquitination is comprised of a sequence of three enzymatic steps, and aberrations in the pathway can lead to tumor development and progression as observed in many cancer types. Recent evidence indicates that targeting the UPS is effective for certain cancer treatment, but many more potential targets might have been previously overlooked. In this review, we will discuss the current state of small molecules that target various elements of ubiquitination. Special attention will be given to novel inhibitors of E3 ubiquitin ligases, especially those in the SCF family.
authors.affiliation: Integrated Molecular Discovery Laboratory, Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX 77030, USA.|The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
authors.forename: John Kenneth
authors.initials: JK
authors.lastname: Morrow
authors.affiliation: Department of Molecular & Cellular Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hui-Kuan
authors.initials: HK
authors.lastname: Lin
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Shao-Cong
authors.initials: SC
authors.lastname: Sun
authors.affiliation: Integrated Molecular Discovery Laboratory, Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Shuxing
authors.initials: S
authors.lastname: Zhang
mesh_terms: D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061988:Proteasome Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054875:Ubiquitination; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D061988:Proteasome Inhibitors; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases
keywords: E3 ligase inhibition; SCF complex; Skp2 inhibitors; cancer therapeutics; deubiquitinase; high-throughput virtual screening; hot spots; in silico modeling; small molecule inhibitors; ubiquitination