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Gene Review

Tpr  -  translocated promoter region, nuclear...

Mus musculus

Synonyms: 2610029M07Rik, C77892, NPC-associated intranuclear protein, Nucleoprotein TPR, Translocated promoter region and nuclear basket protein
 
 
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Disease relevance of Tpr

  • Pretreatment of both Tpr-Met-transformed NIH3T3 fibroblasts and of GTL-16 gastric carcinoma cells with K252a results in loss of their ability to form lung metastases in nude mice upon injection into the caudal vein [1].
 

High impact information on Tpr

 

Biological context of Tpr

  • A Met-hepatocyte growth factor receptor oncoprotein, Tpr-Met, generated by chromosomal rearrangement, fuses a protein dimerization motif with the cytoplasmic domain of the Met receptor, producing a cytosolic, constitutively activated tyrosine kinase [4].
  • Thus, although the three Met oncogenes examined are similar in their dependency on a number of specific tyrosines for activity, the signaling strategy employed by Tpr-Met can be differentiated from that of the other two [7].
  • Similarly, activating mutations introduced into a constitutively dimerized cytoplasmic form of Met (i.e. Tpr-Met) facilitate its autophosphorylation and oncogenic activity in the absence of Y8,9 phosphorylation [8].
 

Anatomical context of Tpr

 

Associations of Tpr with chemical compounds

 

Analytical, diagnostic and therapeutic context of Tpr

  • Accordingly, novel antibodies against the N- and C-terminus of Tpr identified the full-length protein as the major translation product in different somatic cell types; reinvestigation of Tpr localization by confocal microscopy corroborated a predominant localization at the nuclear pore complexes in these cells [11].
  • Immunoprecipitation of Tpr from 32P-orthophosphate-labeled cells shows that it is a phosphoprotein [12].
  • Anti-Tpr polyclonal monospecific antibodies (Ab) used for immunofluorescence staining labeled the nuclear envelope (NE) in a punctate pattern characteristic of nucleoporins and also yielded staining throughout the nuclear interior [6].

References

  1. K252a inhibits the oncogenic properties of Met, the HGF receptor. Morotti, A., Mila, S., Accornero, P., Tagliabue, E., Ponzetto, C. Oncogene (2002) [Pubmed]
  2. Polyglutamine expansion of huntingtin impairs its nuclear export. Cornett, J., Cao, F., Wang, C.E., Ross, C.A., Bates, G.P., Li, S.H., Li, X.J. Nat. Genet. (2005) [Pubmed]
  3. Identification of protein p270/Tpr as a constitutive component of the nuclear pore complex-attached intranuclear filaments. Cordes, V.C., Reidenbach, S., Rackwitz, H.R., Franke, W.W. J. Cell Biol. (1997) [Pubmed]
  4. Enhanced transformation by a plasma membrane-associated met oncoprotein: activation of a phosphoinositide 3'-kinase-dependent autocrine loop involving hyaluronic acid and CD44. Kamikura, D.M., Khoury, H., Maroun, C., Naujokas, M.A., Park, M. Mol. Cell. Biol. (2000) [Pubmed]
  5. Dimerization mediated through a leucine zipper activates the oncogenic potential of the met receptor tyrosine kinase. Rodrigues, G.A., Park, M. Mol. Cell. Biol. (1993) [Pubmed]
  6. The mouse interferon-inducible gene Ifi204 product interacts with the Tpr protein, a component of the nuclear pore complex. De Andrea, M., Zannetti, C., Noris, E., Gariglio, M., Azzimonti, B., Landolfo, S. J. Interferon Cytokine Res. (2002) [Pubmed]
  7. Signaling requirements for oncogenic forms of the Met tyrosine kinase receptor. Jeffers, M., Koochekpour, S., Fiscella, M., Sathyanarayana, B.K., Vande Woude, G.F. Oncogene (1998) [Pubmed]
  8. Activating mutations in the Met receptor overcome the requirement for autophosphorylation of tyrosines crucial for wild type signaling. Jeffers, M.F. Oncogene (1999) [Pubmed]
  9. Regulation of the urokinase-type plasminogen activator gene by the oncogene Tpr-Met involves GRB2. Besser, D., Bardelli, A., Didichenko, S., Thelen, M., Comoglio, P.M., Ponzetto, C., Nagamine, Y. Oncogene (1997) [Pubmed]
  10. SU5416 is a potent inhibitor of hepatocyte growth factor receptor (c-Met) and blocks HGF-induced invasiveness of human HepG2 hepatoma cells. Wang, S.Y., Chen, B., Zhan, Y.Q., Xu, W.X., Li, C.Y., Yang, R.F., Zheng, H., Yue, P.B., Larsen, S.H., Sun, H.B., Yang, X. J. Hepatol. (2004) [Pubmed]
  11. The evolutionarily conserved single-copy gene for murine Tpr encodes one prevalent isoform in somatic cells and lacks paralogs in higher eukaryotes. Kuznetsov, N.V., Sandblad, L., Hase, M.E., Hunziker, A., Hergt, M., Cordes, V.C. Chromosoma (2002) [Pubmed]
  12. Product of the oncogene-activating gene Tpr is a phosphorylated protein of the nuclear pore complex. Bangs, P.L., Sparks, C.A., Odgren, P.R., Fey, E.G. J. Cell. Biochem. (1996) [Pubmed]
 
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