The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

FT-0670698     (2S)-2-acetamido-3- [(2R,3S,4R)-3-hydroxy-2...

Synonyms: AC1L2Y08
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of AIDS-008388


Psychiatry related information on AIDS-008388

  • We report here that the addition of MG132 or lactacystin, each a specific inhibitor of cellular proteasome activity, preferentially enhances cellular permissiveness to infection by Nef-defective versus wild-type HIV-1 [6].
  • Bilateral infusion of lactacystin, a specific proteasome inhibitor, to the CA1 region caused full retrograde amnesia for a one-trial inhibitory avoidance learning when given 1, 4 or 7h, but not 10 h, after training [7].

High impact information on AIDS-008388

  • None of five other proteases were inhibited, and the ability of lactacystin analogs to inhibit cell cycle progression and induce neurite outgrowth correlated with their ability to inhibit the proteasome [1].
  • Tritium-labeled lactacystin was used to identify the 20S proteasome as its specific cellular target [1].
  • Three distinct peptidase activities of this enzyme complex (trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing activities) were inhibited by lactacystin, the first two irreversibly and all at different rates [1].
  • We demonstrate that Dd targeted to the cytosol does not generate the Qa-1b peptide epitope even in the presence of lactacystin [8].
  • Treatment with the proteasome inhibitors lactacystin or epoxomicin reversed m155 down-regulation of H60 [9].

Chemical compound and disease context of AIDS-008388


Biological context of AIDS-008388


Anatomical context of AIDS-008388

  • Degradation apparently occurs within lysosomes, as it is prevented by cysteine protease inhibitors such as E64, but not by the proteasome inhibitor lactacystin [19].
  • The current study examined EC lateral junction proteins, principally the vascular endothelial (VE)-cadherin complex and the effects of proteasome inhibitors (MG132 and lactacystin) on lateral junctions during leukocyte adhesion, to gain a better understanding of the role of EC junctions in leukocyte transmigration [20].
  • This order of events was confirmed in macrophages where lactacystin inhibited the proteolytic activation of precursor ICE and the subsequent generation of active interleukin-1beta [21].
  • Neurite outgrowth in response to lactacystin appears to be dependent upon microtubule assembly, actin polymerization, and de novo protein synthesis [3].
  • Between 1 and 10 microM, the mildly cytotoxic lactacystin inhibited the AICD of DO.11.10 cells cultured in anti-CD3-coated wells [16].

Associations of AIDS-008388 with other chemical compounds


Gene context of AIDS-008388

  • This decrease was reversed by the proteasome inhibitors MG132 and lactacystin, by p19(arf), and by small interfering RNA (siRNA) against MDM2. p21waf1/cip1 bound to MDM2 in vitro and in cells [25].
  • Degradation of IkappaBbeta and the translocation of the NF-kappaB (p50/RelA) into the nucleus, which occurred at 1.5 hr after anti-CD3 activation, were inhibited by lactacystin [16].
  • This effect was linked to a posttranscriptional mechanism involving enhanced iNOS protein degradation by the proteasome pathway, because (i) induction of iNOS mRNA by cytokines was not affected and (ii) iNOS protein levels increased in the presence of the proteasome inhibitors N-acetyl-Leu-Leu-Norleucinal and lactacystin [26].
  • In addition, lactacystin failed to inhibit the killing of DO.11.10 by FasL-expressing allo-specific cytotoxic effector cells [16].
  • However, the MDM2 protein could be easily detected after treatment of cells with the specific proteasome inhibitor lactacystin, suggesting a normal regulation of the p53-MDM2 regulating loop [27].

Analytical, diagnostic and therapeutic context of AIDS-008388

  • The response to lactacystin involves induction of a predominantly bipolar morphology that is maximal 16-32 h after treatment and is distinct from the response to several other treatments that result in morphological differentiation [3].
  • Immunofluorescence analyses of endogenous TR in the growth hormone-producing GC cells showed that the T3-induced rapid degradation of TR was specifically blocked by lactacystin, a selective inhibitor of the ubiquitin-proteasome degradation pathway [28].
  • Furthermore, lactacystin effectively enhanced the antitumor activity of etoposide in the refractory HT-29 xenograft [29].
  • These results indicate that lactacystin could serve as a new therapeutic agent to circumvent resistance to topo II-targeted chemotherapy in solid tumors [29].
  • Inhibition of proteasomal degradation with lactacystin restored L18A/L25A protein expression, although this channel was not expressed at the cell surface as assessed by cell surface immunoprecipitation and whole-cell patch clamp [30].


  1. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Fenteany, G., Standaert, R.F., Lane, W.S., Choi, S., Corey, E.J., Schreiber, S.L. Science (1995) [Pubmed]
  2. Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3. Valmori, D., Gileadi, U., Servis, C., Dunbar, P.R., Cerottini, J.C., Romero, P., Cerundolo, V., Lévy, F. J. Exp. Med. (1999) [Pubmed]
  3. A beta-lactone related to lactacystin induces neurite outgrowth in a neuroblastoma cell line and inhibits cell cycle progression in an osteosarcoma cell line. Fenteany, G., Standaert, R.F., Reichard, G.A., Corey, E.J., Schreiber, S.L. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  4. Involvement of the ubiquitin-proteasome pathway and molecular chaperones in oculopharyngeal muscular dystrophy. Abu-Baker, A., Messaed, C., Laganiere, J., Gaspar, C., Brais, B., Rouleau, G.A. Hum. Mol. Genet. (2003) [Pubmed]
  5. Deregulation of the ubiquitin system and p53 proteolysis modify the apoptotic response in B-CLL lymphocytes. Masdehors, P., Merle-Béral, H., Maloum, K., Omura, S., Magdelénat, H., Delic, J. Blood (2000) [Pubmed]
  6. Selective restriction of Nef-defective human immunodeficiency virus type 1 by a proteasome-dependent mechanism. Qi, M., Aiken, C. J. Virol. (2007) [Pubmed]
  7. The ubiquitin-proteasome cascade is required for mammalian long-term memory formation. Lopez-Salon, M., Alonso, M., Vianna, M.R., Viola, H., Mello e Souza, T., Izquierdo, I., Pasquini, J.M., Medina, J.H. Eur. J. Neurosci. (2001) [Pubmed]
  8. The pathway for processing leader-derived peptides that regulate the maturation and expression of Qa-1b. Bai, A., Broen, J., Forman, J. Immunity (1998) [Pubmed]
  9. The cytomegalovirus m155 gene product subverts natural killer cell antiviral protection by disruption of H60-NKG2D interactions. Lodoen, M.B., Abenes, G., Umamoto, S., Houchins, J.P., Liu, F., Lanier, L.L. J. Exp. Med. (2004) [Pubmed]
  10. Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Qin, J.Z., Ziffra, J., Stennett, L., Bodner, B., Bonish, B.K., Chaturvedi, V., Bennett, F., Pollock, P.M., Trent, J.M., Hendrix, M.J., Rizzo, P., Miele, L., Nickoloff, B.J. Cancer Res. (2005) [Pubmed]
  11. Secreted proteins from Mycobacterium tuberculosis gain access to the cytosolic MHC class-I antigen-processing pathway. Lewinsohn, D.M., Grotzke, J.E., Heinzel, A.S., Zhu, L., Ovendale, P.J., Johnson, M., Alderson, M.R. J. Immunol. (2006) [Pubmed]
  12. Retinoic acid mediates degradation of IRS-1 by the ubiquitin-proteasome pathway, via a PKC-dependant mechanism. del Rincón, S.V., Guo, Q., Morelli, C., Shiu, H.Y., Surmacz, E., Miller, W.H. Oncogene (2004) [Pubmed]
  13. Tau is not normally degraded by the proteasome. Feuillette, S., Blard, O., Lecourtois, M., Frébourg, T., Campion, D., Dumanchin, C. J. Neurosci. Res. (2005) [Pubmed]
  14. Inhibition of Human Preadipocyte Proteasomal Activity by HIV Protease Inhibitors or Specific Inhibitor Lactacystin Leads to a Defect in Adipogenesis, Which Involves Matrix Metalloproteinase-9. De Barros, S., Zakaroff-Girard, A., Lafontan, M., Galitzky, J., Bourlier, V. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  15. The proteolysis of mitotic cyclins in mammalian cells persists from the end of mitosis until the onset of S phase. Brandeis, M., Hunt, T. EMBO J. (1996) [Pubmed]
  16. Proteasome regulation of activation-induced T cell death. Cui, H., Matsui, K., Omura, S., Schauer, S.L., Matulka, R.A., Sonenshein, G.E., Ju, S.T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  17. Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein. Goletz, T.J., Klimpel, K.R., Arora, N., Leppla, S.H., Keith, J.M., Berzofsky, J.A. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  18. Two distinct proteolytic processes in the generation of a major histocompatibility complex class I-presented peptide. Craiu, A., Akopian, T., Goldberg, A., Rock, K.L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  19. Invariant chain controls H2-M proteolysis in mouse splenocytes and dendritic cells. Pierre, P., Shachar, I., Matza, D., Gatti, E., Flavell, R.A., Mellman, I. J. Exp. Med. (2000) [Pubmed]
  20. Endothelial-dependent mechanisms regulate leukocyte transmigration: a process involving the proteasome and disruption of the vascular endothelial-cadherin complex at endothelial cell-to-cell junctions. Allport, J.R., Ding, H., Collins, T., Gerritsen, M.E., Luscinskas, F.W. J. Exp. Med. (1997) [Pubmed]
  21. Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons. Sadoul, R., Fernandez, P.A., Quiquerez, A.L., Martinou, I., Maki, M., Schröter, M., Becherer, J.D., Irmler, M., Tschopp, J., Martinou, J.C. EMBO J. (1996) [Pubmed]
  22. Regulation of p53 stability and p53-dependent apoptosis by NADH quinone oxidoreductase 1. Asher, G., Lotem, J., Cohen, B., Sachs, L., Shaul, Y. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  23. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Meng, L., Mohan, R., Kwok, B.H., Elofsson, M., Sin, N., Crews, C.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  24. Requirement of ATM in phosphorylation of the human p53 protein at serine 15 following DNA double-strand breaks. Nakagawa, K., Taya, Y., Tamai, K., Yamaizumi, M. Mol. Cell. Biol. (1999) [Pubmed]
  25. MDM2 promotes p21waf1/cip1 proteasomal turnover independently of ubiquitylation. Jin, Y., Lee, H., Zeng, S.X., Dai, M.S., Lu, H. EMBO J. (2003) [Pubmed]
  26. Caveolin-1 down-regulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells. Felley-Bosco, E., Bender, F.C., Courjault-Gautier, F., Bron, C., Quest, A.F. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  27. p53 stabilization and functional impairment in the absence of genetic mutation or the alteration of the p14(ARF)-MDM2 loop in ex vivo and cultured adult T-cell leukemia/lymphoma cells. Takemoto, S., Trovato, R., Cereseto, A., Nicot, C., Kislyakova, T., Casareto, L., Waldmann, T., Torelli, G., Franchini, G. Blood (2000) [Pubmed]
  28. Hormone binding induces rapid proteasome-mediated degradation of thyroid hormone receptors. Dace, A., Zhao, L., Park, K.S., Furuno, T., Takamura, N., Nakanishi, M., West, B.L., Hanover, J.A., Cheng, S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  29. Proteasome inhibition circumvents solid tumor resistance to topoisomerase II-directed drugs. Ogiso, Y., Tomida, A., Lei, S., Omura, S., Tsuruo, T. Cancer Res. (2000) [Pubmed]
  30. Role of the NH2 terminus in the assembly and trafficking of the intermediate conductance Ca2+-activated K+ channel hIK1. Jones, H.M., Hamilton, K.L., Papworth, G.D., Syme, C.A., Watkins, S.C., Bradbury, N.A., Devor, D.C. J. Biol. Chem. (2004) [Pubmed]
WikiGenes - Universities