TRIB3 (TRB3)

TRIB3 disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. TRIB3 may bind directly to and mask the 'Thr-308' phosphorylation site in AKT1. TRIB3 binds to ATF4 and inhibits its transcriptional activation activity. TRIB3 interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. TRIB3 interacts with MAPK kinases and regulates activation of MAP kinases. TRIB3 may play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. TRIB3 does not display kinase activity.

TRIB3 (TRB3) Related Areas

Enzyme>>Protein Kinase>>Intracellular Kinase>>TRIB3/TRB3

Signal Transduction>>Protein Kinase>>Intracellular Kinase>>TRIB3/TRB3

TRIB3 (TRB3) Alternative Names

TRIB3, TRB3, TRB-3, RP5-1103G7.7, C20orf97, NIPK, SINK, SKIP3 [Homo sapiens]

TRIB3, Trb3, TRB-3, RP23-396N8.1, Ifld2, Nipk, SINK, SKIP3 [Mus musculus]

Summaries for TRIB3 (TRB3)

Entrez Gene summary for TRIB3 (TRB3):

The protein encoded by TRIB3 gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1. [provided by RefSeq, Jul 2008]

Wikipedia summary for TRIB3 (TRB3):

Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene.
The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB, and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1.

Human TRIB3 (TRB3) Protein General Information

 

• Protein names: Tribbles homolog 3
  Short name=TRB-3
• Sequence length: 358 AA.
• Induction: By hypoxia, TNF and by nutrient starvation. Expression is PI 3-kinase and/or NF-kappa-B-dependent.
• Sequence similarities: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.
  Contains 1 protein kinase domain.
• Caution: The role of this protein in Akt activation has been demonstrated by Du et al (PubMed:12791994) for the mouse ortholog but Iynedjian (PubMed:15469416) has not been able to reproduce the result in rat hepatocytes.
• Subunit structure: Interacts with AKT1, AKT2, ATF4, MAP2K1 and MAP2K7.
• Subcellular location: Nucleus.
• Tissue specificity: Highest expression in liver, pancreas, peripheral blood leukocytes and bone marrow. Also highly expressed in a number of primary lung, colon and breast tumors. Expressed in spleen, thymus, and prostate and is undetectable in other examined tissues, including testis, ovary, small intestine, colon, leukocyte, heart, brain, placenta, lung, skeletal muscle, and kidney.

General information above from UniProt

Function for TRIB3 (TRB3) Protein

UniProtKB:

TRIB3 disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. TRIB3 may bind directly to and mask the 'Thr-308' phosphorylation site in AKT1. TRIB3 binds to ATF4 and inhibits its transcriptional activation activity. TRIB3 interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. TRIB3 interacts with MAPK kinases and regulates activation of MAP kinases. TRIB3 may play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. TRIB3 does not display kinase activity.

Genatlas:

• TRIB3 has a serine/threonine kinase activity
• TRIB3 may play a role in tumor cell growth and neuronal cell death
• TRIB3 is NF-kappaB-inducible protein, inhibiting AKT1 activity by preventing its phosphorylation
• TRIB3 is involved in a novel negative feedback control pathway of NF-kappaB-induced gene expression
• TRIB3 may function as a negative feedback regulator of ATF4
• TRIB3 is novel target of DDIT3/ATF4 and downregulates its own induction by repression of DDIT3/ATF4 functions, and is involved in DDIT3-dependent cell death during ER stress
• TRIB3 acts as a potent negative regulator of PPARgamma, a master regulator of adipocyte differentiation, and tightly controls adipogenesis (Takahashi 2009)
• TRIB3 is key in determining cell fate while responding to environmental challenges (Hegedus 2006)
• TRIB3 protects cells against the growth inhibitory and cytotoxic effect of ATF4 (Ord 2007)
• sTRIB3 is caffold-like regulator of various signal transducers and has been implicated in several processes including insulin signaling, NF-kappaB signaling, lipid metabolism and BMP signaling

Homology for human TRIB3 (TRB3)

• homolog to murine TRB-3
• homolog to rattus Rn.22325
• homolog to Drosophila trbl
• homolog to C8FW