Disease relevance of TRIP6

• By radiation hybrid mapping, the human TRIP6 gene was assigned to a segment of chromosome 7q22 that is commonly deleted in malignant myeloid diseases and uterine leiomyoma [1].
• Overexpression of TRIP6 augments LPA-induced cell migration; in contrast, suppression of endogenous TRIP6 expression by a TRIP6-specific small interfering RNA reduces it in SKOV3 ovarian cancer cells [2].
• These data indicate that OIP-1 is a novel, specific inhibitor of osteoclast formation and bone resorption [3].

High impact information on TRIP6

• A candidate clone was identified and isolated from a human osteoclast-like multinucleated cell (MNC) cDNA library, named osteoclast inhibitory peptide-1 (OIP-1), and the cDNA sequence was determined [3].
• TRIP6 partially rescues SV effects on stress fibers and FAs, apparently by mislocating SV away from FAs [4].
• Supervillin modulation of focal adhesions involving TRIP6/ZRP-1 [4].
• Identification, purification, and characterization of a zyxin-related protein that binds the focal adhesion and microfilament protein VASP (vasodilator-stimulated phosphoprotein) [5].
• TRIP6 enhances lysophosphatidic acid-induced cell migration by interacting with the lysophosphatidic acid 2 receptor [2].

Biological context of TRIP6

• Here we report the complete amino acid sequence of human TRIP6 [1].
• Taken together, our results suggest that TRIP6 functions at a point of convergence between the activated LPA(2) receptor and downstream signals involved in cell adhesion and migration [2].
• In the course of our experiments, we also characterized the nuclear export signal of human TRIP6, and show that LIMD1 is localized in focal adhesions [6].
• The genomic organization of the ZRP-1 coding sequence is identical to that of the lipoma preferred partner gene, another Zyxin-related protein, suggesting that the two genes have evolved from a recent gene duplication event [7].
• Taken together, our results indicate that Trip6 may be a protein that is important for the ability of v-Rel to activate transcription and transform cells, and may represent a potential target for blocking Rel-mediated oncogenesis and transcriptional activation [8].

Anatomical context of TRIP6

• In addition, TRIP6 associates with the components of focal complexes including paxillin, focal adhesion kinase, c-Src, and p130(cas) in an agonist-dependent manner [2].
• We previously identified a novel inhibitor of OCL formation that is produced by OCLs (osteoclast inhibitory peptide-1/human Sca [OIP-1/hSca]) [9].
• Immunocytochemical staining further confirmed the expression of OIP-1/hSca in OCL formed in mouse bone marrow cultures [9].
• OIP1 protein localizes to the sperm tail in a pattern expected for an ODF1-interacting protein [10].
• OIP1 is expressed in round spermatids as well as in spermatocytes and several somatic tissues, albeit at a lower level [10].

Associations of TRIP6 with chemical compounds

• The thyroid receptor interacting protein-6 (TRIP6) was first identified as a ligand-dependent binding partner for the thyroid hormone receptor in a yeast two-hybrid screen [1].
• Stat-1 specific inhibitor, fludarabine (50 muM) abolished IFN-gamma stimulated OIP-1 gene promoter activity [11].

Physical interactions of TRIP6

• TRIP6 also interacts with the second out of five PDZ motifs in PTP-BL [12].
• We show that TRIP6 directly binds to the third PDZ domain of Scrib via its carboxy-terminus [6].
• Novel RING finger protein OIP1 binds to conserved amino acid repeats in sperm tail protein ODF1 [10].

Other interactions of TRIP6

• Overexpression of TRIP6 potentiates RIP2-mediated NF-kappaB activation in a dose-dependent manner [13].
• Taken together, PTP-BL, RIL and TRIP6 may function as components of multi-protein complexes at actin-based sub-cellular structures [12].
• The TRIP6 protein displays a proline-rich N-terminal region linked to three tandemly arrayed C-terminal LIM domains [1].
• By using the yeast two-hybrid system, a specific interaction was identified between the second PDZ domain of the cytosolic protein tyrosine phosphatase hPTP1E and a novel protein, which was termed ZRP-1 to indicate its sequence similarity to the Zyxin protein family [7].
• Here, we describe and characterise the interaction of the RIL PDZ domain with the zyxin-related protein TRIP6, a protein containing three C-terminal LIM domains [12].

Analytical, diagnostic and therapeutic context of TRIP6

• In an effort to define the molecular mechanism by which TRIP6 affects cell migration, the yeast two-hybrid assay was employed to identify proteins that directly bind to TRIP6 [14].
• Lastly, Northern blotting shows that Trip6 mRNA is expressed in many human tissues [8].
• Western blot analysis of conditioned media from 293 cells transfected with the OIP-1 cDNA clone confirmed that OIP-1 was released into the media as a membrane-bound GPI-linked protein [3].
• Sequence analysis of OIP-1 gene promoter region further identified a potential Stat-1 binding motif at -1629 to -1639 bp position [11].

References