Skip to main content
SpringerLink
Log in

The IAP Family of Apoptotic Regulators

  • Chapter
Apoptosis: Mechanisms and Role in Disease

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 24))

Abstract

An avalanche of recent discoveries has led to the identification and characterization of the inhibitor of apoptosis (IAP) factors, a family of proteins which has been highly conserved throughout evolution. While relatively little is known about the precise roles of IAPs, the available information suggests that they play an integral role in the programmed cell death pathway. In this chapter we will present a perspective of the discovery and the evolution of our understanding of the IAPs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ahmad M, Srinivasula SM, Wang L, Talanian RV, Litwack G, Fernandes-Alnemri T, Alnemri ES (1997) CRADD, a novel human apoptotic adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting protein RIP. Cancer Res 57:615–619

    PubMed  CAS  Google Scholar 

  • Allison J, Krummel MF (1995) The yin and yan of T cell costimulation. Science 270:932–933

    Article  PubMed  CAS  Google Scholar 

  • Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, surviving expressed in cancer and lymphoma. Nat Med 3:917–921

    Article  PubMed  CAS  Google Scholar 

  • Armitage RJ (1994) Tumor necrosis factor receptor superfamily members and their ligands. Curr Opin Immunol 6:407–413

    Article  PubMed  CAS  Google Scholar 

  • Beg AA, Baltimore D (1996) An essential role for NF-Ï°B in preventing TNF-a-induced cell death. Science 274:782–784

    Article  PubMed  CAS  Google Scholar 

  • Berberich I, Shu G, Siebelt F, Woodgett JR, Kyriakis JM, Clark EA (1996) Cross-linking CD40 on B cells preferentially induces stress-activated protein kinases rather than mitogen-activated protein kinases. EMBO J 15:92–101

    PubMed  CAS  Google Scholar 

  • Blake TJ, Shapiro M, Morse HCD, Langdon WY (1991) 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 6:653–657

    PubMed  CAS  Google Scholar 

  • Borden KL, Boddy MN, Lally J, O’Reilly NJ, Martin S, Howe K, Solomon E, Freemont PS (1995) The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J 14:1532–1541

    PubMed  CAS  Google Scholar 

  • Bump NJ, Hackett M, Hugunin M, Seshagiri S, Brady K, Chen P, Ferenz C, Franklin S, Ghayur T, Li P, Licari P, Mankovich J, Shi L, Greenberg AH, Miller LK, Wong WW (1995) Inhibition of ICE family proteases by baculovirus antiapoptotic protein p35. Science 269:1885–1888

    Article  PubMed  CAS  Google Scholar 

  • Cheng EH-Y, Nicholas J, Bellows DS, Hayward GS, Guo H-G, Reitz MS, Hardwick JM (1997) A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci USA 94:690–694

    Article  PubMed  CAS  Google Scholar 

  • Chu Z-L, McKinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW (1997) Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis C-IAP2 is under NF-xB control. Proc Natl Acad Sci USA 94:10057–10062

    Article  PubMed  CAS  Google Scholar 

  • Clem RJ, Miller LK (1993) Apoptosis reduces both the in vitro replication and the in vivo infectivity of a baculovirus. J Virol 67:3730–3738

    PubMed  CAS  Google Scholar 

  • Clem RJ, Miller LK (1994) Control of programmed cell death by the baculovirus genes p35 and iap. Mol Cell Biol 14:5212–5222

    PubMed  CAS  Google Scholar 

  • Clem RJ, Fechheimer M, Miller LK (1991) Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science 254:1388–1390

    Article  PubMed  CAS  Google Scholar 

  • Crook NE, Clem RJ, Miller LK (1993) An apoptosis-inhibiting baculovirus gene with a zinc fingerlike motif. J Virol 67:2168–2174

    PubMed  CAS  Google Scholar 

  • de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A (1991) The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 66:675–684

    Article  PubMed  Google Scholar 

  • Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) X-linked IAP is a direct inhibitor of cell death proteases. Nature 388:300–304

    Article  PubMed  CAS  Google Scholar 

  • Digby MR, Kimpton WG, York JJ, Connick TE, Lowenthal JW (1996) ITA, a vertebrate homologue of IAP that is expressed in T lymphocytes. DNA Cell Biol 15:981–988

    Article  PubMed  CAS  Google Scholar 

  • Duckett CS, Nava VE, Gedrich RW, Clem RJ, Van Dongen JL, Gilfillan MC, Shiels H, Hardwick JM, Thompson CB (1996) A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J 15:2685–2694

    PubMed  CAS  Google Scholar 

  • Duckett CS, Gedrich RW, Gilfillan MC, Thompson CB (1997) Induction of nuclear factor Ï°B by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol Cell Biol 17:1535–1542

    PubMed  CAS  Google Scholar 

  • Duckett CS, Li F, Wang Y, Tomaselli KJ, Thompson CB, Armstrong RC (1998) Human IAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome c. Mol Cell Biol 18:608–615

    PubMed  CAS  Google Scholar 

  • Foy TM, Aruffo A, Bajorath J, Buhlmann JE, Noëlle RJ (1996) Immune regulation by CD40 and its ligand, gp39. Annu Rev Immunol 14:591–617

    Article  PubMed  CAS  Google Scholar 

  • Gerasimova TI, Gdula DA, Gerasimov DV, Simonova O, Corces VG (1995) A Drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variega tion. Cell 82:587–597

    Article  PubMed  CAS  Google Scholar 

  • Harvey AJ, Bidwai AP, Miller LK (1996) Doom, a product of the Drosophila mod(mdg4) gene, induces apoptosis and binds to baculovirus inhibitor of apoptosis proteins. Mol Cell Biol 17:2835–2843

    Google Scholar 

  • Hawkins CJ, Uren AG, Hacker G, Medcalf RL, Vaux DL (1996) Inhibition of interleukin 1β- converting enzyme-mediated apoptosis of mammalian cells by baculovirus IAP. Proc Natl Acad Sci USA 93:13786–13790

    Article  PubMed  CAS  Google Scholar 

  • Hay BA, Wassarman DA, Rubin GM (1995) Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. Cell 83:1253–1262

    Article  Google Scholar 

  • Henderson S, Huen D, Rowe M, Dawson C, Johnson G, Rickinson A (1993) Epstein-Barr virus- coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death. Proc Natl Acad Sci USA 90:8479–8483

    Article  PubMed  CAS  Google Scholar 

  • Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide- ranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  PubMed  CAS  Google Scholar 

  • Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, et al. (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80:155–165

    Article  PubMed  CAS  Google Scholar 

  • Liston P, Roy N, Tamai K, Lefebvre C, Baird S, Cherton-Horvat G, Farahani R, McLean M, Ikeda J-E, MacKenzie A, Korneluk RG (1996) Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379:349–353

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996a) Induction of apoptotic program in cell- free extracts: requirement for dATP and cytochrome c. Cell 86:147–157

    Article  PubMed  CAS  Google Scholar 

  • Liu ZG, Hsu H, Goeddel DV, Karin M (1996b) Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis, while NF-xB activation prevents cell death. Cell 87:565–576

    Article  PubMed  CAS  Google Scholar 

  • Macen JL, Garner RS, Musy PY, Brooks MA, Turner PC, Moyer RW, McFadden G, Bleackley RC (1996) Differential inhibition of the Fas- and granule-mediated cytolysis pathways by the orthopoxvirus cytokine response modifier A/SPI-2 and SPI-1 protein. Proc Natl Acad Sci USA 93:9108–9113

    Article  PubMed  CAS  Google Scholar 

  • Orth K, Dixit VM (1997) Bik and Bak induce apoptosis downstream of CrmA but upstream of inhibitor of apoptosis. J Biol Chem 272:8841–8844

    Article  PubMed  CAS  Google Scholar 

  • Rothe M, Wong SC, Henzel WJ, Goeddel DV (1994) A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 78:681–692

    Article  PubMed  CAS  Google Scholar 

  • Rothe M, Pan M-G, Henzel WJ, Ayres TM, Goeddel DV (1995a) The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 83:1243–1252

    Article  PubMed  CAS  Google Scholar 

  • Rothe M, Sarma V, Dixit VM, Goeddel DV (1995b) TRAF2-mediated activation of NF-xB by TNF receptor 2 and CD40. Science 269:1424–1427

    Article  PubMed  CAS  Google Scholar 

  • Roy N, Mahadevan MS, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, Besner-Johnston A, Lefebvre C, Kang X, Salih M, Aubry H, Tamai K, Guan X, Ioannou P, Crawford TO, de Jong PJ, Surh L, Ikeda J-E, Korneluk RG, MacKenzie A (1995) The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 80:167–178

    Article  PubMed  CAS  Google Scholar 

  • Schreiber M, Sedger L, McFadden G (1997) Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor homolog, mediate extracellular TNF binding and intracellular apoptosis inhibition. J Virol 71:2171–2181

    PubMed  CAS  Google Scholar 

  • Shen Y, Shenk TE (1995) Viruses and apoptosis. Curr Opin Gen Dev 5:105–111

    Article  CAS  Google Scholar 

  • Shu H-B, Takeuchi M, Goeddel DV (1996) The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAPl are components of the tumor necrosis factor receptor 1 signaling complex. Proc Natl Acad Sci USA 93:13973–13978

    Article  PubMed  CAS  Google Scholar 

  • Smith CA, Farrah T, Goodwin RG (1994) The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 76:959–962

    Article  PubMed  CAS  Google Scholar 

  • Susin SA, Zamzani N, Castedo M, Hirsch T, Marchetti P, Macho A, Daugas E, Geuskens M, Kroemer G (1996) Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J Exp Med 184:1331–1341

    Article  PubMed  CAS  Google Scholar 

  • Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schröter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386:517–521

    Article  PubMed  CAS  Google Scholar 

  • Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456–1462

    Article  PubMed  CAS  Google Scholar 

  • Upton C, Macen JL, Schreiber M, McFadden G (1991) Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence. Virology 184:370–382

    Article  PubMed  CAS  Google Scholar 

  • Uren A, Pakusch M, Hawkins C, Puls KL, Vaux DL (1996) Cloning and expression of apoptosis inhibitory proteins homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc Natl Acad Sci USA 93:4974–4978

    Article  PubMed  CAS  Google Scholar 

  • Van Antwerp DJ, Martin SJ, Kafri T, Green D, Verma IM (1996) Suppression of TNF-a-induced apoptosis by NF-Ï°B. Science 274:787–789

    Article  PubMed  CAS  Google Scholar 

  • Vucic D, Kaiser WJ, Harvey AJ, Miller LK (1997a) Inhibition of reaper-induced apoptosis by interaction with inhibitor of apoptosis proteins (IAPs). Proc Natl Acad Sci USA 94:10183–10188

    Article  PubMed  CAS  Google Scholar 

  • Vucic D, Seshagiri S, Miller LK (1997b) Characterization of Reaper- and FADD-induced apoptosis in a lepidopteran cell line. Mol Cell Biol 17:667–676

    PubMed  CAS  Google Scholar 

  • Wang C-Y, Mayo MW, Baldwin AS (1996) TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-xB. Science 274:784–787

    Article  PubMed  CAS  Google Scholar 

  • Xue D, Horvitz HR (1995) Inhibition of the Caenorhabditis elegans cell-death protease CED-3 by a CED-3 cleavage site in baculovirus p35 protein. Nature 377:248–251

    Article  PubMed  CAS  Google Scholar 

  • Zamzami N, Marchetti P, Castedo M, Decaudin D, Macho A, Hirsch T, Susin SA, Petit PX, Mignotte B, Kroemer G (1995a) Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med 182:367–377

    Article  PubMed  CAS  Google Scholar 

  • Zamzami N, Marchetti P, Castedo M, Zanin C, Vayssiere JL, Petit PX, Kroemer G (1995b) Reduction in mitochondrial potential constitutes an early irreversible step of programmed cell death in vivo. J Exp Med 181:1661–1672

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Metabolism Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 6B-05, Bethesda, Maryland, 20892-1578, USA

    Lisa J. Eiben & Colin S. Duckett

Authors
  1. Lisa J. Eiben
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Colin S. Duckett
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, P. O. Box 14, Rundle Mall, Adelaide, SA, 5000, Australia

    Sharad Kumar

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Eiben, L.J., Duckett, C.S. (1998). The IAP Family of Apoptotic Regulators. In: Kumar, S. (eds) Apoptosis: Mechanisms and Role in Disease. Results and Problems in Cell Differentiation, vol 24. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69185-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-69185-3_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-21625-5

  • Online ISBN: 978-3-540-69185-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation