Cargando…

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

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 l...

Descripción completa

Detalles Bibliográficos
Autores principales: Eyers, Patrick A., Keeshan, Karen, Kannan, Natarajan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Publishers 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382568/
https://www.ncbi.nlm.nih.gov/pubmed/27908682
http://dx.doi.org/10.1016/j.tcb.2016.11.002
_version_ 1782520127253643264
author Eyers, Patrick A.
Keeshan, Karen
Kannan, Natarajan
author_facet Eyers, Patrick A.
Keeshan, Karen
Kannan, Natarajan
author_sort Eyers, Patrick A.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5382568
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Elsevier Science Publishers
record_format MEDLINE/PubMed
spelling pubmed-53825682017-04-12 Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease Eyers, Patrick A. Keeshan, Karen Kannan, Natarajan Trends Cell Biol Review 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. Elsevier Science Publishers 2017-04 /pmc/articles/PMC5382568/ /pubmed/27908682 http://dx.doi.org/10.1016/j.tcb.2016.11.002 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Eyers, Patrick A.
Keeshan, Karen
Kannan, Natarajan
Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease
title Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease
title_full Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease
title_fullStr Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease
title_full_unstemmed Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease
title_short Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease
title_sort tribbles in the 21st century: the evolving roles of tribbles pseudokinases in biology and disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382568/
https://www.ncbi.nlm.nih.gov/pubmed/27908682
http://dx.doi.org/10.1016/j.tcb.2016.11.002
work_keys_str_mv AT eyerspatricka tribblesinthe21stcenturytheevolvingrolesoftribblespseudokinasesinbiologyanddisease
AT keeshankaren tribblesinthe21stcenturytheevolvingrolesoftribblespseudokinasesinbiologyanddisease
AT kannannatarajan tribblesinthe21stcenturytheevolvingrolesoftribblespseudokinasesinbiologyanddisease