Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1995 May 1;14(9):1923–1931. doi: 10.1002/j.1460-2075.1995.tb07184.x

Interleukin-1 beta converting enzyme requires oligomerization for activity of processed forms in vivo.

Y Gu 1, J Wu 1, C Faucheu 1, J L Lalanne 1, A Diu 1, D J Livingston 1, M S Su 1
PMCID: PMC398291  PMID: 7743999

Abstract

Interleukin-1 beta converting enzyme (ICE) is composed of 10' (p10) and 20 kDa (p20) subunits, which are derived from a common 45 kDa precursor. Recent crystallographic studies have shown that ICE exists as a tetramer (p20/p10)2 in the crystal lattice. We provide evidence that the p10 and p20 subunits of ICE associate as oligomers in transfected COS cells. Using intragenic complementation, we show that the activity of a p10/p10 interface mutant defective in autoprocessing can be restored by co-expression with active site ICE mutants. Different active site mutants can also complement each other by oligomerization to form active ICE. These studies indicate that ICE precursor polypeptides may associate in different quaternary structures and that oligomerization is required for autoprocessing. Furthermore, integenic complementation of active site mutants of ICE and an ICE homolog restores autoprocessing activity, suggesting that hetero-oligomerization occurs between ICE homologs.

Full text

PDF
1926

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ayala J. M., Yamin T. T., Egger L. A., Chin J., Kostura M. J., Miller D. K. IL-1 beta-converting enzyme is present in monocytic cells as an inactive 45-kDa precursor. J Immunol. 1994 Sep 15;153(6):2592–2599. [PubMed] [Google Scholar]
  2. Bennett M. J., Choe S., Eisenberg D. Domain swapping: entangling alliances between proteins. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3127–3131. doi: 10.1073/pnas.91.8.3127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Black R. A., Kronheim S. R., Cantrell M., Deeley M. C., March C. J., Prickett K. S., Wignall J., Conlon P. J., Cosman D., Hopp T. P. Generation of biologically active interleukin-1 beta by proteolytic cleavage of the inactive precursor. J Biol Chem. 1988 Jul 5;263(19):9437–9442. [PubMed] [Google Scholar]
  4. Cerretti D. P., Kozlosky C. J., Mosley B., Nelson N., Van Ness K., Greenstreet T. A., March C. J., Kronheim S. R., Druck T., Cannizzaro L. A. Molecular cloning of the interleukin-1 beta converting enzyme. Science. 1992 Apr 3;256(5053):97–100. doi: 10.1126/science.1373520. [DOI] [PubMed] [Google Scholar]
  5. Dinarello C. A., Wolff S. M. The role of interleukin-1 in disease. N Engl J Med. 1993 Jan 14;328(2):106–113. doi: 10.1056/NEJM199301143280207. [DOI] [PubMed] [Google Scholar]
  6. Faucheu C., Diu A., Chan A. W., Blanchet A. M., Miossec C., Hervé F., Collard-Dutilleul V., Gu Y., Aldape R. A., Lippke J. A. A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells. EMBO J. 1995 May 1;14(9):1914–1922. doi: 10.1002/j.1460-2075.1995.tb07183.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Gu Y., Franco A., Jr, Gardner P. D., Lansman J. B., Forsayeth J. R., Hall Z. W. Properties of embryonic and adult muscle acetylcholine receptors transiently expressed in COS cells. Neuron. 1990 Aug;5(2):147–157. doi: 10.1016/0896-6273(90)90305-y. [DOI] [PubMed] [Google Scholar]
  9. Howard A. D., Kostura M. J., Thornberry N., Ding G. J., Limjuco G., Weidner J., Salley J. P., Hogquist K. A., Chaplin D. D., Mumford R. A. IL-1-converting enzyme requires aspartic acid residues for processing of the IL-1 beta precursor at two distinct sites and does not cleave 31-kDa IL-1 alpha. J Immunol. 1991 Nov 1;147(9):2964–2969. [PubMed] [Google Scholar]
  10. Kostura M. J., Tocci M. J., Limjuco G., Chin J., Cameron P., Hillman A. G., Chartrain N. A., Schmidt J. A. Identification of a monocyte specific pre-interleukin 1 beta convertase activity. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5227–5231. doi: 10.1073/pnas.86.14.5227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Molineaux S. M., Casano F. J., Rolando A. M., Peterson E. P., Limjuco G., Chin J., Griffin P. R., Calaycay J. R., Ding G. J., Yamin T. T. Interleukin 1 beta (IL-1 beta) processing in murine macrophages requires a structurally conserved homologue of human IL-1 beta converting enzyme. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1809–1813. doi: 10.1073/pnas.90.5.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nett M. A., Cerretti D. P., Berson D. R., Seavitt J., Gilbert D. J., Jenkins N. A., Copeland N. G., Black R. A., Chaplin D. D. Molecular cloning of the murine IL-1 beta converting enzyme cDNA. J Immunol. 1992 Nov 15;149(10):3254–3259. [PubMed] [Google Scholar]
  16. 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]
  17. Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y. The structure, expression, and properties of additional members of the protein kinase C family. J Biol Chem. 1988 May 15;263(14):6927–6932. [PubMed] [Google Scholar]
  18. Piccoli R., Tamburrini M., Piccialli G., Di Donato A., Parente A., D'Alessio G. The dual-mode quaternary structure of seminal RNase. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1870–1874. doi: 10.1073/pnas.89.5.1870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ray C. A., Black R. A., Kronheim S. R., Greenstreet T. A., Sleath P. R., Salvesen G. S., Pickup D. J. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell. 1992 May 15;69(4):597–604. doi: 10.1016/0092-8674(92)90223-y. [DOI] [PubMed] [Google Scholar]
  20. Sleath P. R., Hendrickson R. C., Kronheim S. R., March C. J., Black R. A. Substrate specificity of the protease that processes human interleukin-1 beta. J Biol Chem. 1990 Aug 25;265(24):14526–14528. [PubMed] [Google Scholar]
  21. Takebe Y., Seiki M., Fujisawa J., Hoy P., Yokota K., Arai K., Yoshida M., Arai N. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988 Jan;8(1):466–472. doi: 10.1128/mcb.8.1.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thornberry N. A., Bull H. G., Calaycay J. R., Chapman K. T., Howard A. D., Kostura M. J., Miller D. K., Molineaux S. M., Weidner J. R., Aunins J. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992 Apr 30;356(6372):768–774. doi: 10.1038/356768a0. [DOI] [PubMed] [Google Scholar]
  23. Tsai D. E., Kenan D. J., Keene J. D. In vitro selection of an RNA epitope immunologically cross-reactive with a peptide. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8864–8868. doi: 10.1073/pnas.89.19.8864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vaux D. L., Weissman I. L., Kim S. K. Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science. 1992 Dec 18;258(5090):1955–1957. doi: 10.1126/science.1470921. [DOI] [PubMed] [Google Scholar]
  25. Walker N. P., Talanian R. V., Brady K. D., Dang L. C., Bump N. J., Ferenz C. R., Franklin S., Ghayur T., Hackett M. C., Hammill L. D. Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer. Cell. 1994 Jul 29;78(2):343–352. doi: 10.1016/0092-8674(94)90303-4. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Wilson K. P., Black J. A., Thomson J. A., Kim E. E., Griffith J. P., Navia M. A., Murcko M. A., Chambers S. P., Aldape R. A., Raybuck S. A. Structure and mechanism of interleukin-1 beta converting enzyme. Nature. 1994 Jul 28;370(6487):270–275. doi: 10.1038/370270a0. [DOI] [PubMed] [Google Scholar]
  28. 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]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES