Tribbles in the 21st Century: the evolving roles of Tribbles pseudokinases in biology and disease

Eyers, P. A., Keeshan, K. and Kannan, N. (2017) Tribbles in the 21st Century: the evolving roles of Tribbles pseudokinases in biology and disease. Trends in Cell Biology, 27(4), pp. 284-298. (doi: 10.1016/j.tcb.2016.11.002) (PMID:27908682) (PMCID:PMC5382568)

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Abstract

The Tribbles (TRIB) pseudokinases control multiple aspects of eukaryotic cell biology and evolved unique features distinguishing them from all other protein kinases. The atypical pseudokinase domain retains a regulated binding platform for substrates, which are ubiquitinated by context-specific E3 ligases. This plastic configuration has also been exploited as a scaffold to support the modulation of canonical MAPK and AKT modules. In this review, we discuss the evolution of TRIBs and their roles in vertebrate cell biology. TRIB2 is the most ancestral member of the family, whereas the emergence of TRIB3 homologs in mammals supports additional biological roles, many of which are currently being dissected. Given their pleiotropic role in diseases, the unusual TRIB pseudokinase conformation provides a highly attractive opportunity for drug design.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Keeshan, Dr Karen
Authors: Eyers, P. A., Keeshan, K., and Kannan, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Trends in Cell Biology
Publisher:Elsevier (Cell Press)
ISSN:0962-8924
ISSN (Online):1879-3088
Published Online:28 November 2016
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Trends in Cell Biology 27(4): 284-298
Publisher Policy:Reproduced under a creative commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
623941Targeting Trib2 oncogenic signalling in normal and malignant stem cells.Karen KeeshanBloodwise (BLOODWIS)13011RI CANCER SCIENCES