Tribbles: novel regulators of cell function; evolutionary aspects

Hegedűs, Zoltán; Czibula, Ágnes; Kiss-Tóth, Endre

doi:10.1007/s00018-006-6007-9

Cited by 90 publications

(64 citation statements)

References 45 publications

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“…Using a literature gene-set comparison approach for late graft injury, we identified TRIB1, a human homolog of Drosophila tribbles, [15][16][17] as a potentially informative biomarker. TRIB1 is a scarcely characterized member of the tribbles family (see references 22,23 for review) that has been shown to be a potent regulator of cell signaling 18 in various cells lines. We thus explored the potential of TRIB1 as a tissue, peripheral blood, and urine biomarker by measuring its mRNA profiles in graft biopsies, blood, and urine from healthy volunteers and kidney transplant recipients with different histologic and/or clinical diagnoses.…”

Section: Discussionmentioning

confidence: 99%

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Tribbles-1 as a Novel Biomarker of Chronic Antibody-Mediated Rejection

Ashton‐Chess

Giral

Mengel³

et al. 2008

Journal of the American Society of Nephrology

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Diagnosis of the specific cause of late allograft injury is necessary if more personalized and efficient immunosuppressive regimens are to be introduced. This study sought previously unrecognized biomarkers for specific histologic diagnoses of late graft scarring by comparison of gene sets from published microarray studies. Tribbles-1 (TRIB1), a human homolog of Drosophila tribbles, was identified to be a potentially informative biomarker. For testing this, mRNA expression in 76 graft biopsies, 71 blood samples, and 11 urine samples were profiled from independent cohorts of renal transplant patients with different histologic diagnoses recruited at two European centers. TRIB1 but not TRIB2 or TRIB3 was found to be a potential blood and tissue biomarker of chronic antibody-mediated rejection, an active immune-mediated form of chronic allograft failure associated with a poor prognosis. TRIB1 mRNA levels in peripheral blood mononuclear cells discriminated patients with chronic antibody-mediated rejection from those with other types of late allograft injury with high sensitivity and specificity. TRIB1 was also upregulated in a rodent model of chronic cardiac vasculopathy, suggesting that this biomarker may be useful in other solid-organ transplants and across species. It was determined that TRIB1 is expressed primarily by antigen-presenting cells and activated endothelial cells. Overall, these data support the potential use of TRIB1 as a biomarker of chronic antibody-mediated allograft failure.

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Section: Discussionmentioning

confidence: 99%

“…Part of this study was presented as an abstract at the World Transplant Congress (Boston, MA; July [22][23][24][25][26][27] 2006) and at the American Transplant Congress (San Francisco, CA; May 5-9, 2007).…”

Section: Acknowledgmentsmentioning

confidence: 99%

Tribbles-1 as a Novel Biomarker of Chronic Antibody-Mediated Rejection

Ashton‐Chess

Giral

Mengel³

et al. 2008

Journal of the American Society of Nephrology

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“…In contrast, the Trib domain includes a degenerate LRD motif (HRD) in the potential catalytic site but completely lacks the VAIK and DFG domains (Hegedus et al, 2006; Fig. 2B).…”

Section: Developmental Dynamicsmentioning

confidence: 99%

Developmental roles of tribbles protein family members

Dobens

Bouyain

2012

Developmental Dynamics

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The gene tribbles (trbl), identified 12 years ago in genetic screens for mutations that control both cell division and cell migration during embryonic Drosophila development, is the founding member of the Tribbles (Trib) family of kinase-like proteins that have diverse roles in cell signaling, tissue homeostasis, and cancer. Trib proteins share three motifs: (1) a divergent kinase region (Trib domain) with undetermined catalytic activity, (2) a COP1 site used to direct key target proteins to the proteosome for degradation, and (3) a MEK1 site that binds and modulates MAPKK kinase activity. The notion that Tribs act as scaffolding proteins to balance signaling levels in multiple pathways retains an attractive simplicity, but given recent data showing that divergent kinases act by means of novel catalytic mechanisms, the enzymatic activity of Tribs remains untested. Here, we focus on the role of Tribs during development. Developmental analysis of Drosophila trbl phenotypes reveals tissue-specific, sometimes contradictory roles. In mammals, multiple Trib isoforms exhibit overlapping and tissue-specific functions. Recent data indicate the mechanism of Trib activity is conserved and requires the Trib domain. Finally, we discuss the connections between Tribs in disease and cancer that have implications for their normal roles during organogenesis.

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“…TRIB1 is located on chromosome 8q24 and regulates mitogen-activated protein kinase (MAPK) as a presumed adaptor or scaffolding protein (Kiss-Toth et al 2004;Hegedus et al 2006). TRIB1 regulates vascular smooth muscle cell proliferation and chemotaxis via the Jun kinase pathway and is selectively overexpressed in chronically inflamed human atherosclerotic arteries, which suggests that TRIB1 may play an important role in the atherosclerotic process (Sung et al 2007).…”

Section: Introductionmentioning

confidence: 99%

The A>T Polymorphism of the Tribbles Homolog 1 Gene Is Associated with Serum Triglyceride Concentrations in Japanese Community-Dwelling Women

Ikeoka

Hayashida

Nakazato

et al. 2014

Tohoku J. Exp. Med.

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Recent genome-wide association studies have identified Tribbles homolog 1 (TRIB1) as one of the candidate genes associated with lipid profiles. TRIB1 is known to interact with MAP kinases, thereby regulating their activities. The single nucleotide polymorphism rs2954029 of TRIB1 is located within an intron and is associated with lipid profiles. The aim of the present study is to investigate the TRIB1 rs2954029 (A>T polymorphism) with conventional predictors of coronary artery diseases such as carotid intima-media thickness (CIMT) and cardio-ankle vascular index (CAVI), and with lipid profiles in general population. This study enrolled 2,581 Japanese adults, 942 men and 1,639 women with a median age of 68 years (range 29 to 94 years), who participated in a screening program for the general population living in Goto City, Nagasaki Prefecture, Japan from 2008 to 2010. For the determination of TRIB1 rs2954029 genotypes, the polymerase chain reaction method was used. The differences in each parameter among the TRIB1 rs2954029 genotypes were evaluated using analysis of covariance. Genotype frequencies of TRIB1 rs2954029 in all participants were 25.5% for AA, 50.4% for AT, and 24.0% for TT. In women, the AA genotype showed significantly higher log triglyceride (TG) concentrations than the AT genotype (P = 0.004) and the AT + TT genotypes (P = 0.004). On the other hand, there were no associations with CIMT and CAVI among the TRIB1 rs2954029 genotypes. In conclusion, the TRIB1 rs2954029 is associated with serum TG concentrations in Japanese community-dwelling women.

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Tribbles: novel regulators of cell function; evolutionary aspects

Cited by 90 publications

References 45 publications

Tribbles-1 as a Novel Biomarker of Chronic Antibody-Mediated Rejection

Tribbles-1 as a Novel Biomarker of Chronic Antibody-Mediated Rejection

Developmental roles of tribbles protein family members

The A>T Polymorphism of the Tribbles Homolog 1 Gene Is Associated with Serum Triglyceride Concentrations in Japanese Community-Dwelling Women

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