Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease

Eyers, Patrick A ORCID: 0000-0002-9220-2966, Keeshan, Karen and Kannan, Natarajan (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.

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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:	Article
Uncontrolled Keywords:	Animals, Humans, Neoplasms, Disease, Evolution, Molecular, Signal Transduction, Amino Acid Sequence, Protein Serine-Threonine Kinases
Depositing User:	Symplectic Admin
Date Deposited:	27 Jan 2017 09:32
Last Modified:	19 Jan 2023 07:20
DOI:	10.1016/j.tcb.2016.11.002
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3005400