Title:Mammalian Pseudokinase TRIB3 in Normal Physiology and Disease: Charting the Progress in Old and New Avenues
Volume: 18
Issue: 8
Author(s): Tiit Ord*Tonis Ord*
Affiliation:
- Estonian Biocentre, Riia 23b, 51010 Tartu,Estonia
- Estonian Biocentre, Riia 23b, 51010 Tartu,Estonia
Keywords:
TRB3, gene regulation, cell viability, tumorigenesis, integrated stress response.
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.
