Drug Resist Updat 2002 Dec;5(6):249-58 Links
Cell cycle regulatory E3 ubiquitin ligases as anticancer targets.
Pray TR, Parlati F, Huang J, Wong BR, Payan DG, Bennett MK, Issakani SD, Molineaux S, Demo SD.
Rigel Pharmaceuticals, Inc., 240 East Grand Avenue, South San Francisco, 94080, California, CA, USA
Disregulation of the cell cycle and proliferation play key roles in cellular transformation and tumorigenesis. Such processes are intimately tied to the concentration, localization and activity of enzymes, adapters, receptors, and structural proteins in cells. Ubiquitination of these cellular regulatory proteins, governed by specific enzymes in the ubiquitin (Ub) conjugation cascade, has profound effects on their various functions, most commonly through proteasome targeting and degradation. This review will focus on a variety of E3 Ub ligases as potential oncology drug targets, with particular emphasis on the role of these molecules in the regulation of stability, localization, and activity of key proteins such as tumor suppressors and oncoproteins. E3 ubiquitin ligases that have established roles in cell cycle and apoptosis, such as the anaphase-promoting complex (APC), the Skp-1-Cul1-F-box class, and the murine double minute 2 (MDM2) protein, in addition to more recently discovered E3 ubiquitin ligases which may be similarly important in tumorigenesis, (e.g. Smurf family, CHFR, and Efp), will be discussed. We will present evidence to support E3 ligases as good biological targets in the development of anticancer therapeutics and address challenges in drug discovery for these targets.
Does this paper and its placement support the claimed leadership?
"Rigel entered into a research collaboration with Daiichi Parmaceuticals Co., Ltd. to discover and develop new oncology therapeutics in the area of protein degradation, a field related to Rigel's proprietary ligase program. This agreement represents the first industry collaboration in ligase-related research, showcasing Rigel's lead in this emerging area of cancer drug development." |
