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. 1996 Jun 3;15(11):2685–2694.

A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors.

C S Duckett 1, V E Nava 1, R W Gedrich 1, R J Clem 1, J L Van Dongen 1, M C Gilfillan 1, H Shiels 1, J M Hardwick 1, C B Thompson 1
PMCID: PMC450204  PMID: 8654366

Abstract

The baculovirus inhibitor of apoptosis gene, iap, can impede cell death in insect cells. Here we show that iap can also prevent cell death in mammalian cells. The ability of iap to regulate programmed cell death in widely divergent species raised the possibility that cellular homologs of iap might exist. Consistent with this hypothesis, we have isolated Drosophila and human genes which encode IAP-like proteins (dILP and hILP). Like IAP, both dILP and hILP contain amino-terminal baculovirus IAP repeats (BIRs) and carboxy-terminal RING finger domains. Human ilp encodes a widely expressed cytoplasmic protein that can suppress apoptosis in transfected cells. An analysis of the expressed sequence tag database suggests that hilp is one of several human genes related to iap. Together these data suggest that iap and related cellular genes play an evolutionarily conserved role in the regulation of apoptosis.

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Selected References

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  1. Beidler D. R., Tewari M., Friesen P. D., Poirier G., Dixit V. M. The baculovirus p35 protein inhibits Fas- and tumor necrosis factor-induced apoptosis. J Biol Chem. 1995 Jul 14;270(28):16526–16528. doi: 10.1074/jbc.270.28.16526. [DOI] [PubMed] [Google Scholar]
  2. Birnbaum M. J., Clem R. J., Miller L. K. An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs. J Virol. 1994 Apr;68(4):2521–2528. doi: 10.1128/jvi.68.4.2521-2528.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bishop J. M. Molecular themes in oncogenesis. Cell. 1991 Jan 25;64(2):235–248. doi: 10.1016/0092-8674(91)90636-d. [DOI] [PubMed] [Google Scholar]
  4. Blake T. J., Shapiro M., Morse H. C., 3rd, Langdon W. Y. The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif. Oncogene. 1991 Apr;6(4):653–657. [PubMed] [Google Scholar]
  5. Boise L. H., González-García M., Postema C. E., Ding L., Lindsten T., Turka L. A., Mao X., Nuñez G., Thompson C. B. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell. 1993 Aug 27;74(4):597–608. doi: 10.1016/0092-8674(93)90508-n. [DOI] [PubMed] [Google Scholar]
  6. Borden K. L., Boddy M. N., Lally J., O'Reilly N. J., Martin S., Howe K., Solomon E., Freemont P. S. The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J. 1995 Apr 3;14(7):1532–1541. doi: 10.1002/j.1460-2075.1995.tb07139.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bump N. J., Hackett M., Hugunin M., Seshagiri S., Brady K., Chen P., Ferenz C., Franklin S., Ghayur T., Li P. Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35. Science. 1995 Sep 29;269(5232):1885–1888. doi: 10.1126/science.7569933. [DOI] [PubMed] [Google Scholar]
  8. Cavener D. R., Ray S. C. Eukaryotic start and stop translation sites. Nucleic Acids Res. 1991 Jun 25;19(12):3185–3192. doi: 10.1093/nar/19.12.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cheng G., Cleary A. M., Ye Z. S., Hong D. I., Lederman S., Baltimore D. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science. 1995 Mar 10;267(5203):1494–1498. doi: 10.1126/science.7533327. [DOI] [PubMed] [Google Scholar]
  10. Chiou S. K., Tseng C. C., Rao L., White E. Functional complementation of the adenovirus E1B 19-kilodalton protein with Bcl-2 in the inhibition of apoptosis in infected cells. J Virol. 1994 Oct;68(10):6553–6566. doi: 10.1128/jvi.68.10.6553-6566.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Clem R. J., Fechheimer M., Miller L. K. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science. 1991 Nov 29;254(5036):1388–1390. doi: 10.1126/science.1962198. [DOI] [PubMed] [Google Scholar]
  12. Clem R. J., Miller L. K. Apoptosis reduces both the in vitro replication and the in vivo infectivity of a baculovirus. J Virol. 1993 Jul;67(7):3730–3738. doi: 10.1128/jvi.67.7.3730-3738.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Clem R. J., Miller L. K. Control of programmed cell death by the baculovirus genes p35 and iap. Mol Cell Biol. 1994 Aug;14(8):5212–5222. doi: 10.1128/mcb.14.8.5212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Crook N. E., Clem R. J., Miller L. K. An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J Virol. 1993 Apr;67(4):2168–2174. doi: 10.1128/jvi.67.4.2168-2174.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Debbas M., White E. Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev. 1993 Apr;7(4):546–554. doi: 10.1101/gad.7.4.546. [DOI] [PubMed] [Google Scholar]
  16. Duckett C. S., Perkins N. D., Kowalik T. F., Schmid R. M., Huang E. S., Baldwin A. S., Jr, Nabel G. J. Dimerization of NF-KB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an I kappa B-alpha (MAD-3). Mol Cell Biol. 1993 Mar;13(3):1315–1322. doi: 10.1128/mcb.13.3.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Farrow S. N., White J. H., Martinou I., Raven T., Pun K. T., Grinham C. J., Martinou J. C., Brown R. Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K. Nature. 1995 Apr 20;374(6524):731–733. doi: 10.1038/374731a0. [DOI] [PubMed] [Google Scholar]
  18. Fernandes-Alnemri T., Litwack G., Alnemri E. S. Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family. Cancer Res. 1995 Jul 1;55(13):2737–2742. [PubMed] [Google Scholar]
  19. Friesen P. D., Miller L. K. Divergent transcription of early 35- and 94-kilodalton protein genes encoded by the HindIII K genome fragment of the baculovirus Autographa californica nuclear polyhedrosis virus. J Virol. 1987 Jul;61(7):2264–2272. doi: 10.1128/jvi.61.7.2264-2272.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gagliardini V., Fernandez P. A., Lee R. K., Drexler H. C., Rotello R. J., Fishman M. C., Yuan J. Prevention of vertebrate neuronal death by the crmA gene. Science. 1994 Feb 11;263(5148):826–828. doi: 10.1126/science.8303301. [DOI] [PubMed] [Google Scholar]
  21. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Henderson S., Huen D., Rowe M., Dawson C., Johnson G., Rickinson A. Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8479–8483. doi: 10.1073/pnas.90.18.8479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hershberger P. A., Dickson J. A., Friesen P. D. Site-specific mutagenesis of the 35-kilodalton protein gene encoded by Autographa californica nuclear polyhedrosis virus: cell line-specific effects on virus replication. J Virol. 1992 Sep;66(9):5525–5533. doi: 10.1128/jvi.66.9.5525-5533.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hershberger P. A., LaCount D. J., Friesen P. D. The apoptotic suppressor P35 is required early during baculovirus replication and is targeted to the cytosol of infected cells. J Virol. 1994 Jun;68(6):3467–3477. doi: 10.1128/jvi.68.6.3467-3477.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hertz J. M., Huang H. V. Utilization of heterologous alphavirus junction sequences as promoters by Sindbis virus. J Virol. 1992 Feb;66(2):857–864. doi: 10.1128/jvi.66.2.857-864.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hsiao K. A fast and simple procedure for sequencing double stranded DNA with sequenase. Nucleic Acids Res. 1991 May 25;19(10):2787–2787. doi: 10.1093/nar/19.10.2787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hu H. M., O'Rourke K., Boguski M. S., Dixit V. M. A novel RING finger protein interacts with the cytoplasmic domain of CD40. J Biol Chem. 1994 Dec 2;269(48):30069–30072. [PubMed] [Google Scholar]
  28. June C. H., Ledbetter J. A., Gillespie M. M., Lindsten T., Thompson C. B. T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol. 1987 Dec;7(12):4472–4481. doi: 10.1128/mcb.7.12.4472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kamita S. G., Majima K., Maeda S. Identification and characterization of the p35 gene of Bombyx mori nuclear polyhedrosis virus that prevents virus-induced apoptosis. J Virol. 1993 Jan;67(1):455–463. doi: 10.1128/jvi.67.1.455-463.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Komiyama T., Ray C. A., Pickup D. J., Howard A. D., Thornberry N. A., Peterson E. P., Salvesen G. Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition. J Biol Chem. 1994 Jul 29;269(30):19331–19337. [PubMed] [Google Scholar]
  31. Kumar S., Kinoshita M., Noda M., Copeland N. G., Jenkins N. A. Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme. Genes Dev. 1994 Jul 15;8(14):1613–1626. doi: 10.1101/gad.8.14.1613. [DOI] [PubMed] [Google Scholar]
  32. Levine B., Huang Q., Isaacs J. T., Reed J. C., Griffin D. E., Hardwick J. M. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature. 1993 Feb 25;361(6414):739–742. doi: 10.1038/361739a0. [DOI] [PubMed] [Google Scholar]
  33. Los M., Van de Craen M., Penning L. C., Schenk H., Westendorp M., Baeuerle P. A., Dröge W., Krammer P. H., Fiers W., Schulze-Osthoff K. Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis. Nature. 1995 May 4;375(6526):81–83. doi: 10.1038/375081a0. [DOI] [PubMed] [Google Scholar]
  34. Lovering R., Hanson I. M., Borden K. L., Martin S., O'Reilly N. J., Evan G. I., Rahman D., Pappin D. J., Trowsdale J., Freemont P. S. Identification and preliminary characterization of a protein motif related to the zinc finger. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2112–2116. doi: 10.1073/pnas.90.6.2112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lustig S., Jackson A. C., Hahn C. S., Griffin D. E., Strauss E. G., Strauss J. H. Molecular basis of Sindbis virus neurovirulence in mice. J Virol. 1988 Jul;62(7):2329–2336. doi: 10.1128/jvi.62.7.2329-2336.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Miura M., Zhu H., Rotello R., Hartwieg E. A., Yuan J. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell. 1993 Nov 19;75(4):653–660. doi: 10.1016/0092-8674(93)90486-a. [DOI] [PubMed] [Google Scholar]
  37. Oltvai Z. N., Korsmeyer S. J. Checkpoints of dueling dimers foil death wishes. Cell. 1994 Oct 21;79(2):189–192. doi: 10.1016/0092-8674(94)90188-0. [DOI] [PubMed] [Google Scholar]
  38. Perkins N. D., Agranoff A. B., Duckett C. S., Nabel G. J. Transcription factor AP-2 regulates human immunodeficiency virus type 1 gene expression. J Virol. 1994 Oct;68(10):6820–6823. doi: 10.1128/jvi.68.10.6820-6823.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rabizadeh S., LaCount D. J., Friesen P. D., Bredesen D. E. Expression of the baculovirus p35 gene inhibits mammalian neural cell death. J Neurochem. 1993 Dec;61(6):2318–2321. doi: 10.1111/j.1471-4159.1993.tb07477.x. [DOI] [PubMed] [Google Scholar]
  40. Ross J. L., Davis M. B., MacIntyre R. J., McKechnie S. W. A model of the Drosophila melanogaster glycerol-3-phosphate oxidase-encoding gene. Gene. 1994 Feb 25;139(2):219–221. doi: 10.1016/0378-1119(94)90759-5. [DOI] [PubMed] [Google Scholar]
  41. Rothe M., Wong S. C., Henzel W. J., Goeddel D. V. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell. 1994 Aug 26;78(4):681–692. doi: 10.1016/0092-8674(94)90532-0. [DOI] [PubMed] [Google Scholar]
  42. Roy N., Mahadevan M. S., McLean M., Shutler G., Yaraghi Z., Farahani R., Baird S., Besner-Johnston A., Lefebvre C., Kang X. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell. 1995 Jan 13;80(1):167–178. doi: 10.1016/0092-8674(95)90461-1. [DOI] [PubMed] [Google Scholar]
  43. Sabbatini P., Chiou S. K., Rao L., White E. Modulation of p53-mediated transcriptional repression and apoptosis by the adenovirus E1B 19K protein. Mol Cell Biol. 1995 Feb;15(2):1060–1070. doi: 10.1128/mcb.15.2.1060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sato T., Irie S., Reed J. C. A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40. FEBS Lett. 1995 Jan 23;358(2):113–118. doi: 10.1016/0014-5793(94)01406-q. [DOI] [PubMed] [Google Scholar]
  45. Song H. Y., Donner D. B. Association of a RING finger protein with the cytoplasmic domain of the human type-2 tumour necrosis factor receptor. Biochem J. 1995 Aug 1;309(Pt 3):825–829. doi: 10.1042/bj3090825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tewari M., Dixit V. M. Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product. J Biol Chem. 1995 Feb 17;270(7):3255–3260. doi: 10.1074/jbc.270.7.3255. [DOI] [PubMed] [Google Scholar]
  47. Tewari M., Quan L. T., O'Rourke K., Desnoyers S., Zeng Z., Beidler D. R., Poirier G. G., Salvesen G. S., Dixit V. M. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 1995 Jun 2;81(5):801–809. doi: 10.1016/0092-8674(95)90541-3. [DOI] [PubMed] [Google Scholar]
  48. Vaux D. L., Haecker G., Strasser A. An evolutionary perspective on apoptosis. Cell. 1994 Mar 11;76(5):777–779. doi: 10.1016/0092-8674(94)90350-6. [DOI] [PubMed] [Google Scholar]
  49. Wang L., Miura M., Bergeron L., Zhu H., Yuan J. Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell. 1994 Sep 9;78(5):739–750. doi: 10.1016/s0092-8674(94)90422-7. [DOI] [PubMed] [Google Scholar]
  50. White E. Death-defying acts: a meeting review on apoptosis. Genes Dev. 1993 Dec;7(12A):2277–2284. doi: 10.1101/gad.7.12a.2277. [DOI] [PubMed] [Google Scholar]
  51. White K., Grether M. E., Abrams J. M., Young L., Farrell K., Steller H. Genetic control of programmed cell death in Drosophila. Science. 1994 Apr 29;264(5159):677–683. doi: 10.1126/science.8171319. [DOI] [PubMed] [Google Scholar]
  52. Xue D., Horvitz H. R. Inhibition of the Caenorhabditis elegans cell-death protease CED-3 by a CED-3 cleavage site in baculovirus p35 protein. Nature. 1995 Sep 21;377(6546):248–251. doi: 10.1038/377248a0. [DOI] [PubMed] [Google Scholar]
  53. Yuan J., Shaham S., Ledoux S., Ellis H. M., Horvitz H. R. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell. 1993 Nov 19;75(4):641–652. doi: 10.1016/0092-8674(93)90485-9. [DOI] [PubMed] [Google Scholar]
  54. de Thé H., Lavau C., Marchio A., Chomienne C., Degos L., Dejean A. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell. 1991 Aug 23;66(4):675–684. doi: 10.1016/0092-8674(91)90113-d. [DOI] [PubMed] [Google Scholar]

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