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Gene Review

ATG5  -  autophagy related 5

Homo sapiens

Synonyms: APG5, APG5-LIKE, APG5-like, APG5L, ASP, ...
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Disease relevance of ATG5


High impact information on ATG5

  • As the p53-dependent apoptosis pathway is not well understood, we sought to identify apoptosis-specific p53 target genes using a subtractive cloning strategy [6].
  • Recent studies examining cells lacking the autophagy genes Atg5 and Atg7 have demonstrated that autophagy plays essential roles in cell survival during starvation, in innate cell clearance of microbial pathogens, and in neural cell maintenance [7].
  • In the periphery, Atg5(-/-) CD8(+) T lymphocytes displayed dramatically increased cell death [7].
  • A critical role for the autophagy gene Atg5 in T cell survival and proliferation [7].
  • However, the numbers of total thymocytes and peripheral T and B lymphocytes were reduced in Atg5 chimeras [7].

Chemical compound and disease context of ATG5


Biological context of ATG5


Anatomical context of ATG5

  • Furthermore, a potent stimulating activity for ATG12-ATG5 conjugation was detected in mammalian cell extracts, and was surprisingly identified as ribosomes [9].
  • Furthermore, Atg5(-/-) CD4(+) and CD8(+) T cells failed to undergo efficient proliferation after TCR stimulation [7].
  • Truncated Atg5 translocated from the cytosol to mitochondria, associated with the anti-apoptotic molecule Bcl-x(L) and triggered cytochrome c release and caspase activation [13].
  • Furthermore, the induced phosphatase activity coimmunoprecipitated with the hyperphosphorylated RB and was active in a cell-free system that reproduced the growth arrest- and apoptosis-specific RB dephosphorylation, which was inhibitable by calyculin A but not zinc [14].
  • The viability of the T cells cocultured with the HIV-1-infected macrophage cell lines or the primary monocytes as determined by propidium iodide staining was unaltered and there was no increase in apoptosis-specific DNA strand breaks or increased expression of Bcl-2 in the T cells [15].

Associations of ATG5 with chemical compounds

  • This non-apoptotic death of double knockout cells was suppressed by inhibitors of autophagy, including 3-methyl adenine, was dependent on autophagic proteins APG5 and Beclin 1 (capable of binding to Bcl-2/Bcl-x(L)), and was also modulated by Bcl-x(L) [16].
  • Data were confirmed by apoptosis-specific fluorescence-activated cell sorter analysis of confluent HUVEC cultures, which displayed after long-term exposure to 30 mmol/l glucose a 1.5-fold higher prevalence of apoptosis than control cultures exposed to 5 mmol/l glucose (P < 0.005) [17].
  • Treatment of tumour cells with hyperforin resulted in a dose-dependent generation of apoptotic oligonucleosomes, typical DNA-laddering and apoptosis-specific morphological changes [18].
  • Several hallmarks of apoptosis, including DNA laddering, chromatin condensation and fragmentation, and an apoptosis specific cleavage of 28S and 18S ribosomal RNA were observed after treatment with curcumin [19].
  • Bisbenzimide staining of the fixed cells revealed typical apoptotic structures (apoptotic bodies), and the apoptosis-specific "DNA ladder pattern" resulting from internucleosomal cleavage was identified by gel electrophoresis [20].

Regulatory relationships of ATG5


Other interactions of ATG5


Analytical, diagnostic and therapeutic context of ATG5


  1. Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease. Rosen, A., Casciola-Rosen, L. Cell Death Differ. (1999) [Pubmed]
  2. Hypertrophic scar cells fail to undergo a form of apoptosis specific to contractile collagen-the role of tissue transglutaminase. Linge, C., Richardson, J., Vigor, C., Clayton, E., Hardas, B., Rolfe, K. J. Invest. Dermatol. (2005) [Pubmed]
  3. Apoptosis incidence and protein expression of p53, TGF-beta receptor II, p27Kip1, and Smad4 in benign, premalignant, and malignant human prostate. Zeng, L., Rowland, R.G., Lele, S.M., Kyprianou, N. Hum. Pathol. (2004) [Pubmed]
  4. Apoptosis-associated cleavage of beta-catenin in human colon cancer and rat hepatoma cells. Fukuda, K. Int. J. Biochem. Cell Biol. (1999) [Pubmed]
  5. Elevated serum levels of epithelial cell apoptosis-specific cytokeratin 18 neoepitope m30 in critically ill patients. Roth, G.A., Krenn, C., Brunner, M., Moser, B., Ploder, M., Spittler, A., Pelinka, L., Sautner, T., Wolner, E., Boltz-Nitulescu, G., Ankersmit, H.J. Shock (2004) [Pubmed]
  6. PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Attardi, L.D., Reczek, E.E., Cosmas, C., Demicco, E.G., McCurrach, M.E., Lowe, S.W., Jacks, T. Genes Dev. (2000) [Pubmed]
  7. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. Pua, H.H., Dzhagalov, I., Chuck, M., Mizushima, N., He, Y.W. J. Exp. Med. (2007) [Pubmed]
  8. Two-dimensional gel analysis of apoptosis-specific p53 isoforms induced by 2-methoxyestradiol in human lung cancer cells. Mukhopadhyay, T., Roth, J.A., Acosta, S.A., Maxwell, S.A. Apoptosis (1998) [Pubmed]
  9. Stimulation of ATG12-ATG5 Conjugation by Ribonucleic Acid. Shao, Y., Gao, Z., Feldman, T., Jiang, X. Autophagy (2007) [Pubmed]
  10. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. Pyo, J.O., Jang, M.H., Kwon, Y.K., Lee, H.J., Jun, J.I., Woo, H.N., Cho, D.H., Choi, B., Lee, H., Kim, J.H., Mizushima, N., Oshumi, Y., Jung, Y.K. J. Biol. Chem. (2005) [Pubmed]
  11. Induction of apoptosis and cytokine gene expression in T-cell lines by sera of patients with systemic lupus erythematosus. Yang, B.C., Wang, Y.S., Lin, L.C., Liu, M.F. Scand. J. Immunol. (1997) [Pubmed]
  12. Assignment of the yeast APG5 human homologue APG5L to chromosome band 6q21 by fluorescence in situ hybridisation. Schmeiser, K., Armstrong, S., Hammond, E.M., Grand, R.J. Cytogenet. Cell Genet. (1999) [Pubmed]
  13. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Yousefi, S., Perozzo, R., Schmid, I., Ziemiecki, A., Schaffner, T., Scapozza, L., Brunner, T., Simon, H.U. Nat. Cell Biol. (2006) [Pubmed]
  14. Induction of a retinoblastoma phosphatase activity by anticancer drugs accompanies p53-independent G1 arrest and apoptosis. Dou, Q.P., An, B., Will, P.L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  15. Altered cytokine production and accessory cell function after HIV-1 infection. Yoo, J., Chen, H., Kraus, T., Hirsch, D., Polyak, S., George, I., Sperber, K. J. Immunol. (1996) [Pubmed]
  16. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Shimizu, S., Kanaseki, T., Mizushima, N., Mizuta, T., Arakawa-Kobayashi, S., Thompson, C.B., Tsujimoto, Y. Nat. Cell Biol. (2004) [Pubmed]
  17. High-glucose--triggered apoptosis in cultured endothelial cells. Baumgartner-Parzer, S.M., Wagner, L., Pettermann, M., Grillari, J., Gessl, A., Waldhäusl, W. Diabetes (1995) [Pubmed]
  18. Inhibition of tumour cell growth by hyperforin, a novel anticancer drug from St. John's wort that acts by induction of apoptosis. Schempp, C.M., Kirkin, V., Simon-Haarhaus, B., Kersten, A., Kiss, J., Termeer, C.C., Gilb, B., Kaufmann, T., Borner, C., Sleeman, J.P., Simon, J.C. Oncogene (2002) [Pubmed]
  19. Differential regulation of p53, c-Myc, Bcl-2 and Bax protein expression during apoptosis induced by widely divergent stimuli in human hepatoblastoma cells. Jiang, M.C., Yang-Yen, H.F., Lin, J.K., Yen, J.J. Oncogene (1996) [Pubmed]
  20. Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. Rahman, Q., Lohani, M., Dopp, E., Pemsel, H., Jonas, L., Weiss, D.G., Schiffmann, D. Environ. Health Perspect. (2002) [Pubmed]
  21. ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Kouroku, Y., Fujita, E., Tanida, I., Ueno, T., Isoai, A., Kumagai, H., Ogawa, S., Kaufman, R.J., Kominami, E., Momoi, T. Cell Death Differ. (2007) [Pubmed]
  22. Buprenorphine hydrochloride induces apoptosis in NG108-15 nerve cells. Kugawa, F., Arae, K., Ueno, A., Aoki, M. Eur. J. Pharmacol. (1998) [Pubmed]
  23. Characterization of the porcine reproductive and respiratory syndrome virus glycoprotein 5 (GP5) in stably expressing cells. Lee, C., Rogan, D., Erickson, L., Zhang, J., Yoo, D. Virus Res. (2004) [Pubmed]
  24. Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Hamacher-Brady, A., Brady, N.R., Logue, S.E., Sayen, M.R., Jinno, M., Kirshenbaum, L.A., Gottlieb, R.A., Gustafsson, A.B. Cell Death Differ. (2007) [Pubmed]
  25. Structure-Function Relationship of Atg12, a Ubiquitin-like Modifier Essential for Autophagy. Hanada, T., Ohsumi, Y. Autophagy. (2005) [Pubmed]
  26. The behavior of SATB1, a MAR-binding protein, in response to apoptosis stimulation. Sun, Y., Wang, T., Su, Y., Yin, Y., Xu, S., Ma, C., Han, X. Cell Biol. Int. (2006) [Pubmed]
  27. Expression, purification and crystallization of the Atg5-Atg16 complex essential for autophagy. Matsushita, M., Suzuki, N.N., Fujioka, Y., Ohsumi, Y., Inagaki, F. Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. (2006) [Pubmed]
  28. Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa. Portera-Cailliau, C., Sung, C.H., Nathans, J., Adler, R. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  29. Antimetabolite-induced apoptosis in Tenon's capsule fibroblasts. Crowston, J.G., Akbar, A.N., Constable, P.H., Occleston, N.L., Daniels, J.T., Khaw, P.T. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
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