Disease relevance of TPR

• Cardiovascular measures (heart period, HP; preejection period, PEP; respiratory sinus arrhythmia, RSA; cardiac output, CO; systolic blood pressure, SBP; diastolic blood pressure, DBP & total peripheral resistance, TPR) were recorded during 4-minute baseline and 4-minute stressor task periods [1].
• Activation of the MET protooncogene by a rearrangement involving the fusion of TPR and MET specific gene sequences has been observed in a human osteosarcoma cell line (HOS) treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) [2].
• Furthermore, an engineered hybrid TPR-ALK protein can transform rodent fibroblasts and produce lymphomas in mice while remaining confined to the cytoplasm [3].
• Expression and characterization of a magnetosome-associated protein, TPR-containing MAM22, in Escherichia coli [4].
• The TPRD gene (tetratricopeptide (TPR) containing Down syndrome gene) is one of the candidate genes in the Down syndrome chromosomal region-1 [5].

High impact information on TPR

• Several classes of protein domains have been identified that are either designed for or are capable of interacting with protein C-termini - these include PDZ and TPR domains [6].
• The PPR motif - a TPR-related motif prevalent in plant organellar proteins [7].
• FKBP51 is composed of three domains: two consecutive FKBP domains and a three-unit repeat of the TPR (tetratricopeptide repeat) domain [8].
• We found that in vitro translated TPR bound to in vitro translated Nup98 and, via Nup98, to Nup96 [9].
• TPR (translocated promoter region) is a protein that forms filamentous structures extending from nuclear pore complexes (NPCs) to intranuclear sites [9].

Chemical compound and disease context of TPR

• At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P < 0.001) [10].

Biological context of TPR

• We show also the involvement of TPR in the generation of another TRK-T oncogene [11].
• The resulting hybrid mRNA contains 598 nucleotides of the TPR gene and 1148 nucleotides of the TRK proto-oncogene [11].
• The thyroid TRK oncogenes are activated by recombination with at least three different genes: the gene coding for tropomyosin and TPR, both on chromosome 1,and TFG on chromosome 3 [12].
• Nifedipine reduced total peripheral resistance (TPR; 1744 +/- 398 versus 1290 +/- 215 dyne-s/cm5) and increased arterial compliance (ACL; 1.234 +/- 0.253 versus 1.776 +/- 0.415 mL/mm Hg) [13].
• With both drugs, changes in MAP were not associated with significant changes in cardiac output (p greater than 0.10 for both drugs), but correlated with changes in systemic resistance (TPR); r = 0.84, p less than 0.001 for AA and r = 0.71, p less than 0.001 for CEI [14].

Anatomical context of TPR

• This characteristic staining pattern of the TPR network was considerably enhanced when a myc-tagged pyruvate kinase-6kDa fusion protein was overexpressed in HeLa cells [9].
• In this paper, we report (1) the cDNA structure of TRK-T2, (2) evidence that TRK-T2 is generated by different rearrangements in two thyroid tumors, and (3) a detailed analysis of the three different TPR/NTRK1 rearrangements [12].
• Collectively, these findings suggest a novel TPR signaling pathway in OLGs and a potential role for this signaling during OLG maturation and myelin production [15].
• Analysis of hybrid cells containing TPR-MET demonstrated that both the upstream and downstream portions of MET are conserved in this rearrangement and that oncogene activation occurred by an insertion of TPR sequences into the MET locus [16].
• Using Western blotting, the temporal patterns of cleavage of three nuclear matrix proteins (lamin B, NUMA and the nucleoporin TPR) were compared in HL60 cells induced to undergo apoptosis after irradiation, heat shock or treatment with etoposide [17].

Associations of TPR with chemical compounds

• Ramipril also decreased TPR (1740 +/- 292 versus 1437 +/- 290 dyne-s/cm5) and increased ACL (1.214 +/- 0.190 versus 1.569 +/- 0.424 mL/mm Hg), but with this agent, the change in arterial compliance was explained solely on the basis of a reduction in distending pressure [13].
• Atenolol, in contrast, did not affect either TPR or ACL [13].
• Despite the well documented involvement of thromboxane A(2) receptor (TPR) signaling in the pathogenesis of thrombotic diseases, there are currently no rationally designed antagonists available for clinical use [18].
• Results suggested that reduction of blood pressure by lofexidine depended on lack of increase in TPR in response to reduction of cardiac output; the hemodynamic pattern of this centrally acting adrenergic blocker closely resembled that reported for beta blockers [19].
• In addition to the NTPase domain, these proteins typically contain DNA-binding or protein-binding domains, superstructure-forming repeats, such as WD40 and TPR, and enzymatic domains involved in signal transduction, including adenylate cyclases and kinases [20].

Other interactions of TPR

• The nucleoporin Nup98 associates with the intranuclear filamentous protein network of TPR [9].
• Alternatively, inhibition of endogenous TPR signaling led to reduced MBP expression [15].
• Although the TPR4 mutant fully complemented the cells, it showed a reduced interaction with FANCA, suggesting that this TPR may also be of functional importance [21].
• Using Saccharomyces cerevisiae two-hybrid screening, we identified tetratricopeptide repeat 1 (TPR1), a 292-amino-acid protein with three TPR motifs, as a Galpha16-binding protein [22].
• We have also observed that LGN, a Galphai-interacting protein with seven TPR motifs, binds Ha-Ras [22].
• These results suggest that HSP mRNA export escapes stress inhibition via HSF1-mediated recruitment of the nuclear pore-associating protein TPR to HSP genes, thereby functionally connecting the first and last nuclear steps of the gene expression pathway, transcription and mRNA export [23].

Analytical, diagnostic and therapeutic context of TPR

• The distance between NTRK1 and its oncogenic partner TPR was determined by two-color fluorescence in situ hybridization and two-dimensional microscopy [24].
• Comparative sequence alignments indicate that members of this protein family contain multiple SH3 and TPR domains that are likely involved in the formation of protein complexes [25].
• Molecular cloning and expression of a transformation-sensitive human protein containing the TPR motif and sharing identity to the stress-inducible yeast protein STI1 [26].
• Characterizations of the VOx/TiO2 catalysts were carried out with XRD, laser Raman spectroscopy, and TPR [27].
• During TM, there was a greater decrease in SBP due to a concomitantly greater decrease in TPR compared with the control group during eyes-closed relaxation (SBP: -3.0 vs. +2.1 mm Hg, p < .04; TPR: -1.0 vs. +0.3 mm Hg/liter per minute, p < .03) [28].

References