Mammalian Pseudokinase TRIB3 in Normal Physiology and Disease: Charting the Progress in Old and New Avenues.

Abstract:

:Tribbles homolog 3 (TRIB3) is a mammalian gene that is upregulated in response to several types of cell death-inducing cellular stress. The TRIB3 protein is a pseudokinase, a protein kinase-like scaffold with impaired catalytic activity. However, research has revealed it to be prolific at forming protein- protein interactions. By binding to and regulating the activity of several key proteins, including the protein kinase Akt and transcription factors ATF4, CHOP and NF-κB, TRIB3 is at a junction of several signaling pathways. This review begins by providing insights into the characteristic protein structure and gene expression regulation mechanisms of TRIB3. Further, the diverse reported molecular roles of TRIB3 as a regulator of cell death, stress responses, inflammation, cell differentiation, protein degradation and other processes are discussed. Special attention is devoted to the involvement of TRIB3 in the pathogenesis of cancer and type 2 diabetes, two fields where TRIB3 has generated particular interest, as well as considerable debate, from a biomedical standpoint. Throughout, emphasis is placed on results obtained from animal models with altered TRIB3 expression (Trib3 knockout or overexpression mice), in order to provide insight into the contributions of TRIB3 to physiology and disease at the organism level.

journal_name

Curr Protein Pept Sci

authors

Ord T,Ord T

doi

10.2174/1389203718666170406124547

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

819-842

issue

8

eissn

1389-2037

issn

1875-5550

pii

CPPS-EPUB-82691

journal_volume

18

pub_type

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