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Gene Review

DLST  -  dihydrolipoamide S-succinyltransferase (E2...

Homo sapiens

Synonyms: 2-oxoglutarate dehydrogenase complex component E2, DLTS, Dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex, Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial, E2K, ...
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Disease relevance of DLST


Psychiatry related information on DLST


High impact information on DLST

  • The core DNA-binding domain, which comprises both the dimerization domain and a helix predicted to bind the inner portion of the EBNA1 DNA recognition element, was remarkably similar to the structure of the papillomavirus E2 protein, despite a complete lack of sequence conservation [8].
  • Hepatitis C virus, the E2 envelope protein, and alpha-interferon resistance [9].
  • Consistent with the hypothesis of selective pressure by the host immune system, the sequence changes occurred almost exclusively within the hypervariable region 1 of the E2 gene and were temporally correlated with antibody seroconversion [10].
  • The papillomavirus E2 protein regulates viral transcription and DNA replication through interactions with cellular and viral proteins [11].
  • The transcriptional enhancer sequences of the papillomaviruses are regulated by trans-acting factors encoded by the viral E2 open reading frame [12].

Chemical compound and disease context of DLST


Biological context of DLST


Anatomical context of DLST

  • Dihydrolipoamide succinyltransferase (DLST) is the core-enzyme of 2-oxoglutarate dehydrogenase complex which is located in mitochondria [20].
  • The DLST gene is a candidate for the AD3 gene since deficiencies in KGDHC activity have been observed in brain tissue and fibroblasts of AD patients [19].
  • The U2OS-ERalpha and U2OS-ERbeta cell lines were treated with Dox and either vehicle control or E2 for 24 h [21].
  • Estrogen (17beta-estradiol, E2) plays pivotal roles in the function and maintenance of the skeleton, including the bone-forming osteoblasts (OBs) [21].
  • A peripheral blood lymphocytes stimulating test (DLST) with TS-1 demonstrated a substantial positive reaction [22].

Associations of DLST with chemical compounds

  • Another candidate is the dihydrolipoyl succinyltransferase (DLST) gene, one of three components of thiamine-dependent mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC), because KGDHC activity is reported reduced in AD patients [6].
  • Very-low-density lipoprotein (VLDL) cholesterol and triglyceride levels were significantly higher in carriers of both apo E2 and apo E4 in white men only [23].
  • Finally, alpha-ketoglutarate dehydrogenase complex-E2 specific affinity-purified antisera did not react on immunoblot with any component enzymes of pyruvate dehydrogenase complex or branched chain alpha-ketoacid dehydrogenase complex.(ABSTRACT TRUNCATED AT 250 WORDS)[13]
  • Using site-directed mutagenesis we demonstrate that an arginine at position 304 of the hE2 protein is responsible for the recognition of specific base pairs at this position [3].
  • Among the PDC components, the activity of the dihydrolipoamide acetyltransferase-E3-binding protein subcomplex (E2-E3BP) only was decreased by HNE [24].

Regulatory relationships of DLST

  • Similarly 76% of the ERbeta-regulated genes were upregulated whereas 24% were inhibited by E2 [21].

Other interactions of DLST

  • The dihydrolipoamide succinyltransferase (DLST) gene of the alpha-ketoglutarate dehydrogenase complex (alpha-KGDC) was isolated from a rat genomic DNA library and sequenced [25].
  • There were no significant gender or age differences in tested genotypic and allelic distribution except for the DLST and apolipoprotein E [26].
  • The functions of E2 are largely mediated through two distinct estrogen receptor isoforms, ERalpha and ERbeta, both of which are expressed in OBs [21].
  • The distinct patterns of E2-dependent gene regulation in the U2OS cells by ERalpha and ERbeta shown here suggest that during OB differentiation, when either isoform dominates, a unique pattern of gene responses will occur, partially due to the differentiation state and the ER isoform present [21].
  • Results demonstrate that the AR activation plays a pivotal role in the inhibitory action of DHEA on the E2-induced MCF-7 growth [27].

Analytical, diagnostic and therapeutic context of DLST


  1. The alpha-ketoglutarate dehydrogenase complex in neurodegeneration. Gibson, G.E., Park, L.C., Sheu, K.F., Blass, J.P., Calingasan, N.Y. Neurochem. Int. (2000) [Pubmed]
  2. Immunoglobulin gene usage and immunohistochemical characteristics of human monoclonal antibodies to the mitochondrial autoantigens of primary biliary cirrhosis induced in the XenoMouse. Sasaki, M., Van De Water, J., Kenny, T.P., Gallo, M.L., Leung, P.S., Nakanuma, Y., Ansari, A.A., Coppel, R.L., Neuberger, J., Gershwin, M.E. Hepatology (2001) [Pubmed]
  3. DNA binding and bending by the human papillomavirus type 16 E2 protein. Recognition of an extended binding site. Thain, A., Webster, K., Emery, D., Clarke, A.R., Gaston, K. J. Biol. Chem. (1997) [Pubmed]
  4. Maple syrup urine disease: domain structure, mutations and exon skipping in the dihydrolipoyl transacylase (E2) component of the branched-chain alpha-keto acid dehydrogenase complex. Chuang, D.T., Fisher, C.W., Lau, K.S., Griffin, T.A., Wynn, R.M., Cox, R.P. Mol. Biol. Med. (1991) [Pubmed]
  5. Truncated product of the bifunctional DLST gene involved in biogenesis of the respiratory chain. Kanamori, T., Nishimaki, K., Asoh, S., Ishibashi, Y., Takata, I., Kuwabara, T., Taira, K., Yamaguchi, H., Sugihara, S., Yamazaki, T., Ihara, Y., Nakano, K., Matuda, S., Ohta, S. EMBO J. (2003) [Pubmed]
  6. No association between DLST gene and Alzheimer's disease or Wernicke-Korsakoff syndrome. Matsushita, S., Arai, H., Yuzuriha, T., Kato, M., Matsui, T., Urakami, K., Higuchi, S. Neurobiol. Aging (2001) [Pubmed]
  7. Structural features of envelope proteins on hepatitis C virus-like particles as determined by anti-envelope monoclonal antibodies and CD81 binding. Triyatni, M., Vergalla, J., Davis, A.R., Hadlock, K.G., Foung, S.K., Liang, T.J. Virology (2002) [Pubmed]
  8. Crystal structure of the DNA-binding domain of the Epstein-Barr virus origin-binding protein EBNA 1. Bochkarev, A., Barwell, J.A., Pfuetzner, R.A., Furey, W., Edwards, A.M., Frappier, L. Cell (1995) [Pubmed]
  9. Hepatitis C virus, the E2 envelope protein, and alpha-interferon resistance. Abid, K., Quadri, R., Negro, F. Science (2000) [Pubmed]
  10. The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Farci, P., Shimoda, A., Coiana, A., Diaz, G., Peddis, G., Melpolder, J.C., Strazzera, A., Chien, D.Y., Munoz, S.J., Balestrieri, A., Purcell, R.H., Alter, H.J. Science (2000) [Pubmed]
  11. Crystal structure of the human papillomavirus type 18 E2 activation domain. Harris, S.F., Botchan, M.R. Science (1999) [Pubmed]
  12. Functional mapping of the human papillomavirus type 11 transcriptional enhancer and its interaction with the trans-acting E2 proteins. Hirochika, H., Hirochika, R., Broker, T.R., Chow, L.T. Genes Dev. (1988) [Pubmed]
  13. Inhibition of alpha-ketoglutarate dehydrogenase activity by a distinct population of autoantibodies recognizing dihydrolipoamide succinyltransferase in primary biliary cirrhosis. Fregeau, D.R., Prindiville, T., Coppel, R.L., Kaplan, M., Dickson, E.R., Gershwin, M.E. Hepatology (1990) [Pubmed]
  14. Dysfunction of mitochondria and oxidative stress in the pathogenesis of Alzheimer's disease: on defects in the cytochrome c oxidase complex and aldehyde detoxification. Ohta, S., Ohsawa, I. J. Alzheimers Dis. (2006) [Pubmed]
  15. A limited form of Wegener's granulomatosis with bronchiolitis obliterans organizing pneumonitis-like variant in an ulcerative colitis patient. Yano, S., Kobayashi, K., Kato, K., Nishimura, K. Intern. Med. (2002) [Pubmed]
  16. Distribution of dihydrolipoamide acetyltransferase (E2) in the liver and portal lymph nodes of patients with primary biliary cirrhosis: an immunohistochemical study. Joplin, R., Lindsay, J.G., Hubscher, S.G., Johnson, G.D., Shaw, J.C., Strain, A.J., Neuberger, J.M. Hepatology (1991) [Pubmed]
  17. HCV E2 glycoprotein: mutagenesis of N-linked glycosylation sites and its effects on E2 expression and processing. Slater-Handshy, T., Droll, D.A., Fan, X., Di Bisceglie, A.M., Chambers, T.J. Virology (2004) [Pubmed]
  18. Modulation by DLST of the genetic risk of Alzheimer's disease in a very elderly population. Sheu, K.F., Brown, A.M., Haroutunian, V., Kristal, B.S., Thaler, H., Lesser, M., Kalaria, R.N., Relkin, N.R., Mohs, R.C., Lilius, L., Lannfelt, L., Blass, J.P. Ann. Neurol. (1999) [Pubmed]
  19. Mutation analysis of the chromosome 14q24.3 dihydrolipoyl succinyltransferase (DLST) gene in patients with early-onset Alzheimer disease. Cruts, M., Backhovens, H., Van Gassen, G., Theuns, J., Wang, S.Y., Wehnert, A., van Duijn, C.M., Karlsson, T., Hofman, A., Adolfsson, R. Neurosci. Lett. (1995) [Pubmed]
  20. A polypeptide derived from mitochondrial dihydrolipoamide succinyltransferase is located on the plasma membrane in skeletal muscle. Matuda, S., Kodama, J., Goshi, N., Takase, C., Nakano, K., Nakagawa, S., Ohta, S. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  21. Estrogen receptor isoform-specific regulation of endogenous gene expression in human osteoblastic cell lines expressing either ERalpha or ERbeta. Monroe, D.G., Getz, B.J., Johnsen, S.A., Riggs, B.L., Khosla, S., Spelsberg, T.C. J. Cell. Biochem. (2003) [Pubmed]
  22. Interstitial pneumonia possibly due to a novel anticancer drug, TS-1: first case report. Kurakawa, E., Kasuga, I., Ishizuka, S., Yoshida, T., Kunisawa, A., Minemura, K., Utsumi, K., Ohyashiki, K. Jpn. J. Clin. Oncol. (2001) [Pubmed]
  23. Association of apolipoprotein E polymorphism with blood lipids and maximal oxygen uptake in the sedentary state and after exercise training in the HERITAGE family study. Leon, A.S., Togashi, K., Rankinen, T., Després, J.P., Rao, D.C., Skinner, J.S., Wilmore, J.H., Bouchard, C. Metab. Clin. Exp. (2004) [Pubmed]
  24. Protection by thiols of the mitochondrial complexes from 4-hydroxy-2-nonenal. Korotchkina, L.G., Yang, H., Tirosh, O., Packer, L., Patel, M.S. Free Radic. Biol. Med. (2001) [Pubmed]
  25. Isolation and sequence analysis of the rat dihydrolipoamide succinyltransferase gene. Nakano, K., Tanabe, M., Nakagawa, S., Ohta, S., Suzuki, S., Shimura, M., Matuda, S. DNA Seq. (2002) [Pubmed]
  26. Distribution of geriatric disease-related genotypes in the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). Shimokata, H., Yamada, Y., Nakagawa, M., Okubo, R., Saido, T., Funakoshi, A., Miyasaka, K., Ohta, S., Tsujimoto, G., Tanaka, M., Ando, F., Niino, N. Journal of epidemiology / Japan Epidemiological Association. (2000) [Pubmed]
  27. Dehydroepiandrosterone antiestrogenic action through androgen receptor in MCF-7 human breast cancer cell line. Boccuzzi, G., Di Monaco, M., Brignardello, E., Leonardi, L., Gatto, V., Pizzini, A., Gallo, M. Anticancer Res. (1993) [Pubmed]
  28. Substantial linkage disequilibrium across the dihydrolipoyl succinyltransferase gene region without Alzheimer's disease association. Brown, A.M., Gordon, D., Lee, H., Caudy, M., Haroutunian, V., Blass, J.P. Neurochem. Res. (2004) [Pubmed]
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