title: 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.
authors.affiliation: Estonian Biocentre, Riia 23b, 51010 Tartu. Estonia.
authors.forename: Tiit
authors.initials: T
authors.lastname: Ord
authors.affiliation: Estonian Biocentre, Riia 23b, 51010 Tartu. Estonia.
authors.forename: Tonis
authors.initials: T
authors.lastname: Ord
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death; D002454:Cell Differentiation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
chemical_list: C497109:ATF4 protein, human; D018797:Cell Cycle Proteins; C497249:DDIT3 protein, human; D016328:NF-kappa B; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: TRB3; cell viability; gene regulation; integrated stress response; tumorigenesis