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Tkt  -  transketolase

Mus musculus

Synonyms: P68, TK, Transketolase, p68
 
 
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Disease relevance of Tkt

  • Our data suggest that TKT deficiency may have clinical significance in humans and raise the possibility that obesity may be treated by partial inhibition of TKT in adipose tissue [1].
  • A third subset of NK cells, termed T killer (TK) cells deriving from cultures of conventional but not nude mouse spleens, mediated spontaneous cytotoxicity of P815 mastocytoma cells, but not of virus-infected targets [2].
  • B2 cells infected with UV-HSV or transfected with the HSV-1 TK gene and maintained in TK-selective medium showed discrete colonies of cells which displayed a normal flat appearance and expressed the viral TK enzyme [3].
  • The TK coding sequence in the cloned fragment has been localized and a smaller recombinant plasmid, pAG0, also carrying an active TK gene, has been constructed to serve as a more convenient vector for transfer, into TK- cells, of genes previously cloned in E. coli [4].
  • Using monoclonal antibodies, we previously detected two forms of transformation-associated proteins (TAPs), P64 and P68, in the rat kidney (6m2) cells transformed by the temperature-sensitive 110-murine sarcoma virus-Moloney-mutant [5].
 

High impact information on Tkt

  • Assays capable of distinguishing between foreign and native TK indicated that at least one of the fetuses with the HSV tk gene had some TK enzyme of the HSV type and, therefore, at least one gene copy that was being accurately transcribed and translated to produce a functional protein, despite the absence of selective pressure [6].
  • Transketolase haploinsufficiency reduces adipose tissue and female fertility in mice [1].
  • No phenotype was observed in the TKT(+/-) cornea, where TKT is especially abundant in wild-type mice [1].
  • Other TKT(+/-) tissues had moderate ( approximately 33%; liver, gonads) or relatively little ( approximately 7 to 18%; eye, kidney, heart, brain) reductions in mass [1].
  • In MBP-TK transgenic mice, oligodendrocyte ablation was selectively induced by FIAU treatment before and during the onset of myelination [7].
 

Chemical compound and disease context of Tkt

 

Biological context of Tkt

 

Anatomical context of Tkt

  • The relationship between overexpression of transketolase and desensitization resistance was evaluated in somatic cell hybrids formed between a desensitization-resistant adrenal cell line and a desensitization-sensitive rat glial cell line [11].
  • Interestingly, in MBP-TK mice treated for 1-20 days with FIAU, despite the ablation of more than 95% of oligodendrocytes, the protein levels of all tested nodal markers was unaltered [7].
  • Second, the pattern of TK enzyme expression during differentiation was analyzed in muscle cells transformed with recombinant TK genes lacking the 3' nontranslated intron [13].
  • They also provide evidence for a potential role of TK and PTP in pancreatic B-cell function [14].
  • RESULTS: SDS-PAGE (-DTT) resolved mouse serum albumin and transketolase and indicated that serum albumin was 13% of the water-soluble protein in whole mouse corneas [15].
 

Associations of Tkt with chemical compounds

 

Other interactions of Tkt

 

Analytical, diagnostic and therapeutic context of Tkt

  • We show here by gene targeting that TKT-null mouse embryos are not viable and that disruption of one TKT allele can cause growth retardation ( approximately 35%) and preferential reduction of adipose tissue ( approximately 77%) [1].
  • Sequence analysis supports the suggestion that present-day TKT and TKT-like genes arose from the duplication of a single common ancestral gene [22].
  • In addition, Southern blot hybridization has been used to demonstrate in vivo complementation of this mutant by wt virus in both peripheral and central nervous system tissues of mice during acute infection and to show that such complementation can result in the establishment and reactivation of latent TK- infection [23].
  • Thus, the overall data presented here demonstrate that TK gene therapy in combination with GM-CSF and IL-2 gene-mediated immunotherapy strategies have important implications in the treatment of breast cancer [24].

References

  1. Transketolase haploinsufficiency reduces adipose tissue and female fertility in mice. Xu, Z.P., Wawrousek, E.F., Piatigorsky, J. Mol. Cell. Biol. (2002) [Pubmed]
  2. On the heterogeneity of murine natural killer cells. Minato, N., Reid, L., Bloom, B.R. J. Exp. Med. (1981) [Pubmed]
  3. Herpes simplex virus (type 1) thymidine kinase gene does not transform cells morphologically. Hampar, B., Derge, J.G., Boyd, A.L., Tainsky, M.A., Showalter, S.D. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  4. Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12. Colbere-Garapin, F., Chousterman, S., Horodniceanu, F., Kourilsky, P., Garapin, A.C. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  5. Overproduction of metalloproteinases by v-mos-transformed rat kidney (6m2) cells. Chan, J.C. Leukemia (1992) [Pubmed]
  6. The human beta-globin gene and a functional viral thymidine kinase gene in developing mice. Wagner, E.F., Stewart, T.A., Mintz, B. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  7. Essential role of oligodendrocytes in the formation and maintenance of central nervous system nodal regions. Mathis, C., Denisenko-Nehrbass, N., Girault, J.A., Borrelli, E. Development (2001) [Pubmed]
  8. The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study. Comín-Anduix, B., Boren, J., Martinez, S., Moro, C., Centelles, J.J., Trebukhina, R., Petushok, N., Lee, W.N., Boros, L.G., Cascante, M. Eur. J. Biochem. (2001) [Pubmed]
  9. The critical influence of temperature upon trifluorothymidine resistance in mouse lymphoma L5178Y/TK 3.7.2C cells. Amacher, D.E., Turner, G.N. Mutat. Res. (1989) [Pubmed]
  10. Detection of mammalian cell mutagens in urine from carcinogen-dosed mice. Amacher, D.E., Turner, G.N., Ellis, J.H. Mutat. Res. (1981) [Pubmed]
  11. Amplification of the transketolase gene in desensitization-resistant mutant Y1 mouse adrenocortical tumor cells. Schimmer, B.P., Tsao, J., Czerwinski, W. J. Biol. Chem. (1996) [Pubmed]
  12. Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation. Boros, L.G., Puigjaner, J., Cascante, M., Lee, W.N., Brandes, J.L., Bassilian, S., Yusuf, F.I., Williams, R.D., Muscarella, P., Melvin, W.S., Schirmer, W.J. Cancer Res. (1997) [Pubmed]
  13. Structural and functional analysis of an alternatively spliced chicken TK messenger RNA. Merrill, G.F., Tufaro, F.D. Nucleic Acids Res. (1986) [Pubmed]
  14. Possible involvement of a tyrosine kinase-dependent pathway in the regulation of phosphoinositide metabolism by vanadate in normal mouse islets. Jonas, J.C., Henquin, J.C. Biochem. J. (1996) [Pubmed]
  15. Serum albumin in mammalian cornea: implications for clinical application. Nees, D.W., Fariss, R.N., Piatigorsky, J. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  16. Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. Gadau, S., Emanueli, C., Van Linthout, S., Graiani, G., Todaro, M., Meloni, M., Campesi, I., Invernici, G., Spillmann, F., Ward, K., Madeddu, P. Diabetologia (2006) [Pubmed]
  17. Ascorbate as a substrate for glycolysis or gluconeogenesis: evidence for an interorgan ascorbate cycle. Braun, L., Puskás, F., Csala, M., Mészáros, G., Mandl, J., Bánhegyi, G. Free Radic. Biol. Med. (1997) [Pubmed]
  18. Kinetic studies of mouse brain transketolase. Blass, J.P., Piacentini, S., Boldizsar, E., Baker, A. J. Neurochem. (1982) [Pubmed]
  19. Long-term effect of maternal obesity on pancreatic beta cells of offspring: reduced beta cell adaptation to high glucose and high-fat diet challenges in adult female mouse offspring. Han, J., Xu, J., Epstein, P.N., Liu, Y.Q. Diabetologia (2005) [Pubmed]
  20. Metallothionein-null mice express altered genes during development. Kimura, T., Oguro, I., Kohroki, J., Takehara, M., Itoh, N., Nakanishi, T., Tanaka, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  21. Contribution of the antibodies response induced by a low virulent Candida albicans strain in protection against systemic candidiasis. Fernández-Arenas, E., Molero, G., Nombela, C., Diez-Orejas, R., Gil, C. Proteomics (2004) [Pubmed]
  22. The mouse transketolase (TKT) gene: cloning, characterization, and functional promoter analysis. Salamon, C., Chervenak, M., Piatigorsky, J., Sax, C.M. Genomics (1998) [Pubmed]
  23. The role of herpes simplex virus type 1 thymidine kinase in pathogenesis. Efstathiou, S., Kemp, S., Darby, G., Minson, A.C. J. Gen. Virol. (1989) [Pubmed]
  24. Efficacy of herpes simplex virus thymidine kinase in combination with cytokine gene therapy in an experimental metastatic breast cancer model. Majumdar, A.S., Zolotorev, A., Samuel, S., Tran, K., Vertin, B., Hall-Meier, M., Antoni, B.A., Adeline, E., Philip, M., Philip, R. Cancer Gene Ther. (2000) [Pubmed]
 
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