Molecular Pathways Targeting NEDD8-Activated Cullin-RING Ligases for the Treatment of Cancer
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GATA4 and GATA5 are Potential Tumor Suppressors and Biomarkers in Colorectal Cancer. Debby M.E.I. Hellebrekers, Marjolein H.F.M. Lentjes, Sandra M. van den Bosch, Veerle Melotte, Kim A.D. Wouters, Kathleen L.J. Daenen, Kim M. Smits, Yoshimitsu Akiyama, Yasuhito Yuasa, Silvia Sanduleanu, Carolina A.J. Khalid-de Bakker, Daisy Jonkers, Matty P. Weijenberg, Joost Louwagie, Wim van Criekinge, Beatriz Carvalho, Gerrit A. Meijer, Stephen B. Baylin, James G. Herman, Adriaan P. de Bruïne, and Manon van Engeland............................................................................................3990
منابع مشابه
Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer.
E3 ubiquitin ligases regulate many dynamic cellular processes important for cancer cell survival. Together with ubiquitin-activating enzyme (E1) and ubiquitin-conjugating enzymes (E2s), E3s catalyze the ubiquitination of numerous protein substrates that are subsequently targeted to the 26S proteasome for degradation. The clinical success of the proteasome inhibitor bortezomib has encouraged the...
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Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit. DCNs are NEDD8 E3 ligases that promote neddylation. Mammalian cells express five DCN-like (DCNL) proteins but little is known about their specific functions or interaction partners. We foun...
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Ubiquitin and ubiquitin-like proteins (UBLs) are directed to targets by cascades of E1, E2, and E3 enzymes. The largest ubiquitin E3 subclass consists of cullin-RING ligases (CRLs), which contain one each of several cullins (CUL1, -2, -3, -4, or -5) and RING proteins (RBX1 or -2). CRLs are activated by ligation of the UBL NEDD8 to a conserved cullin lysine. How is cullin NEDD8ylation specificit...
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The molecular chaperone heat shock protein 90 (HSP90) is required for the activity and stability of its client proteins. Pharmacologic inhibition of HSP90 leads to the ubiquitin-mediated degradation of clients, particularly activated or mutant oncogenic protein kinases. Client ubiquitination occurs via the action of one or more E3 ubiquitin ligases. We sought to identify the role of Cullin-RING...
متن کاملA Ubiquitin-like Protein Unleashes Ubiquitin Ligases
Modification of cullin-RING ubiquitin ligases by the ubiquitin-like molecule Nedd8 promotes substrate ubiquitination. A crystal structure of a cullin modified by Nedd8 recently reported in Cell (Duda et al., 2008) and a biochemical study in Molecular Cell (Saha and Deshaies, 2008) reveal the dramatic impact on the ligase machinery by conjugation of ubiquitin or ubiquitin-like proteins.
متن کاملStructural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation
Cullin-RING ligases (CRLs) comprise the largest ubiquitin E3 subclass, in which a central cullin subunit links a substrate-binding adaptor with an E2-binding RING. Covalent attachment of the ubiquitin-like protein NEDD8 to a conserved C-terminal domain (ctd) lysine stimulates CRL ubiquitination activity and prevents binding of the inhibitor CAND1. Here we report striking conformational rearrang...
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تاریخ انتشار 2009