Aghajan

Alessio Ciulli

Alexander

Amerik

Andrejeva

Andérica-Romero

Angers

Arai

Arkin

Babon

Bedford

Belzile

Bennett

Bloom

Bradsher

Brownell

Buckley

Bulatov

Bullock

Canning

Cardozo

Castro

Ceccarelli

Chamberlain

Chan

Chen

Ciechanover

Cohen

Cope

Deshaies

Dias

Duda

Emil Bulatov

Errington

Feldman

Fischer

Frescas

Furukawa

Galdeano

Ganoth

Genschik

Goldenberg

Groisman

Grossberger

Hayashi

Hershko

Hori

Huang

Huber

Isaacson

Ivan

Iwai

Jackson

Jnoff

Jones

Jäger

Kamitani

Kamura

Katiyar

Kaustov

Kawakami

Kibel

Kile

Kipreos

Kleiger

Komander

Kuhn

Kumar

Lammer

Le Rouzic

In the last decade, the ubiquitin–proteasome system has emerged as a valid target for the development of novel therapeutics. E3 ubiquitin ligases are particularly attractive targets because they confer substrate specificity on the ubiquitin system. CRLs [Cullin–RING (really interesting new gene) E3 ubiquitin ligases] draw particular attention, being the largest family of E3s. The CRLs assemble into functional multisubunit complexes using a repertoire of substrate receptors, adaptors, Cullin scaffolds and RING-box proteins. Drug discovery targeting CRLs is growing in importance due to mounting evidence pointing to significant roles of these enzymes in diverse biological processes and human diseases, including cancer, where CRLs and their substrates often function as tumour suppressors or oncogenes. In the present review, we provide an account of the assembly and structure of CRL complexes, and outline the current state of the field in terms of available knowledge of small-molecule inhibitors and modulators of CRL activity. A comprehensive overview of the reported crystal structures of CRL subunits, components and full-size complexes, alone or with bound small molecules and substrate peptides, is included. This information is providing increasing opportunities to aid the rational structure-based design of chemical probes and potential small-molecule therapeutics targeting CRLs.</jats:p

Crossref

Biochemical Journal

Targeting Cullin–RING E3 ubiquitin ligases for drug discovery: structure, assembly and small-molecule modulation

http://www.biochemj.org/content/ppbiochemj/467/3/365.full.pdf

Targeting Cullin–RING E3 ubiquitin ligases for drug discovery: structure, assembly and small-molecule modulation

Abstract

Similar works

Full text

Available Versions

Crossref