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PMID: 9878060 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Boo, a novel negative regulator of cell death, interacts with Apaf-1.

The EMBO journal ·Vol. 18 ·No. 1 ·1999-01-04 ·Pages 167-78

Song Q, Kuang Y, Dixit VM, Vincenz C

Abstract

In this report, we describe the cloning and characterization of Boo, a novel anti-apoptotic member of the Bcl-2 family. The expression of Boo was highly restricted to the ovary and epididymis implicating it in the control of ovarian atresia and sperm maturation. Boo contains the conserved BH1 and BH2 domains, but lacks the BH3 motif. Like Bcl-2, Boo possesses a hydrophobic C-terminus and localizes to intracellular membranes. Boo also has an N-terminal region with strong homology to the BH4 domain found to be important for the function of some anti-apoptotic Bcl-2 homologues. Chromosomal localization analysis assigned Boo to murine chromosome 9 at band d9. Boo inhibits apoptosis, homodimerizes or heterodimerizes with some death-promoting and -suppressing Bcl-2 family members. More importantly, Boo interacts with Apaf-1 and forms a multimeric protein complex with Apaf-1 and caspase-9. Bak and Bik, two pro-apoptotic homologues disrupt the association of Boo and Apaf-1. Furthermore, Boo binds to three distinct regions of Apaf-1. These results demonstrate the evolutionarily conserved nature of the mechanisms of apoptosis. Like Ced-9, the mammalian homologues Boo and Bcl-xL interact with the human counterpart of Ced-4, Apaf-1, and thereby regulate apoptosis.

MeSH Terms
Amino Acid Sequence Animals Apoptosis/physiology Apoptotic Protease-Activating Factor 1 Caspase 9 Caspases/chemistry,physiology Cell Line Chromosome Mapping Cloning, Molecular Conserved Sequence Dimerization Female Gene Expression Humans In Situ Hybridization, Fluorescence Macromolecular Substances Male Mice Molecular Sequence Data Ovary/cytology,metabolism Proteins/chemistry,physiology Proto-Oncogene Proteins c-bcl-2/chemistry,genetics,physiology Sequence Homology, Amino Acid Spermatozoa/growth & development,metabolism
Chemicals
APAF1 protein, human Apaf1 protein, mouse Apoptotic Protease-Activating Factor 1 BCL2-like 10 protein Macromolecular Substances Proteins Proto-Oncogene Proteins c-bcl-2 CASP9 protein, human Casp9 protein, mouse Caspase 9 Caspases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Song Q
Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Kuang Y
Dixit V M
Vincenz C
References (65)
65 references, click to expand
  1. The cell-death machine.
    Curr Biol. 1996 May 1;6(5):555-62 PMID: 8805273
  2. The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4.
    EMBO J. 1998 Feb 16;17(4):1029-39 PMID: 9463381
  3. Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex.
    J Biol Chem. 1998 Mar 6;273(10):5841-5 PMID: 9488720
  4. Testicular degeneration in Bclw-deficient mice.
    Nat Genet. 1998 Mar;18(3):251-6 PMID: 9500547
  5. 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):641-52 PMID: 8242740
  6. Bcl-2 and the regulation of programmed cell death.
    J Cell Biol. 1994 Jan;124(1-2):1-6 PMID: 8294493
  7. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2.
    Cell. 1994 Feb 25;76(4):665-76 PMID: 7907274
  8. An evolutionary perspective on apoptosis.
    Cell. 1994 Mar 11;76(5):777-9 PMID: 8124715
  9. Radiation-induced changes in long-term survivors of childhood cancer after treatment with radiation therapy.
    Semin Roentgenol. 1994 Jan;29(1):6-14 PMID: 7510420
  10. Ultrastructure of human ovarian primordial follicles after combination chemotherapy for Hodgkin's disease.
    Hum Reprod. 1993 Dec;8(12):2080-7 PMID: 8150906
  11. Activation of C. elegans cell death protein CED-9 by an amino-acid substitution in a domain conserved in Bcl-2.
    Nature. 1994 May 26;369(6478):318-20 PMID: 7910376
  12. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax.
    Nature. 1994 May 26;369(6478):321-3 PMID: 8183370
  13. Programmed cell death in Caenorhabditis elegans.
    Curr Opin Genet Dev. 1994 Aug;4(4):581-6 PMID: 7950327
  14. Expression of members of the bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased bax and constitutive bcl-2 and bcl-xlong messenger ribonucleic acid levels.
    Endocrinology. 1995 Jan;136(1):232-41 PMID: 7828536
  15. Apoptosis in the pathogenesis and treatment of disease.
    Science. 1995 Mar 10;267(5203):1456-62 PMID: 7878464
  16. Induction of apoptosis by the Bcl-2 homologue Bak.
    Nature. 1995 Apr 20;374(6524):733-6 PMID: 7715730
  17. bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria.
    Development. 1994 Oct;120(10):3033-42 PMID: 7607090
  18. Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad.
    Endocrinology. 1995 Aug;136(8):3665-8 PMID: 7628407
  19. Bcl-2 and Bcl-2-related proteins in apoptosis regulation.
    Curr Top Microbiol Immunol. 1995;200:107-21 PMID: 7634826
  20. Multiple Bcl-2 family members demonstrate selective dimerizations with Bax.
    Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7834-8 PMID: 7644501
  21. Mtd, a novel Bcl-2 family member activates apoptosis in the absence of heterodimerization with Bcl-2 and Bcl-XL.
    J Biol Chem. 1998 Apr 10;273(15):8705-10 PMID: 9535847
  22. Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation.
    Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4386-91 PMID: 9539746
  23. Defects in regulation of apoptosis in caspase-2-deficient mice.
    Genes Dev. 1998 May 1;12(9):1304-14 PMID: 9573047
  24. ERICE, a novel FLICE-activatable caspase.
    J Biol Chem. 1998 Jun 19;273(25):15702-7 PMID: 9624166
  25. Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death.
    J Biol Chem. 1998 Dec 4;273(49):32479-86 PMID: 9829980
  26. Genetic control of programmed cell death in the nematode C. elegans.
    Cell. 1986 Mar 28;44(6):817-29 PMID: 3955651
  27. Social controls on cell survival and cell death.
    Nature. 1992 Apr 2;356(6368):397-400 PMID: 1557121
  28. Caenorhabditis elegans gene ced-9 protects cells from programmed cell death.
    Nature. 1992 Apr 9;356(6369):494-9 PMID: 1560823
  29. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.
    Cell. 1993 Aug 27;74(4):609-19 PMID: 8358790
  30. Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes.
    Cancer Res. 1993 Oct 1;53(19):4701-14 PMID: 8402648
  31. Bax-deficient mice with lymphoid hyperplasia and male germ cell death.
    Science. 1995 Oct 6;270(5233):96-9 PMID: 7569956
  32. Role of multiple cellular proteases in the execution of programmed cell death.
    FEBS Lett. 1995 Nov 20;375(3):169-73 PMID: 7498492
  33. New members of the Bcl-2 family and their protein partners.
    Curr Opin Genet Dev. 1996 Feb;6(1):45-9 PMID: 8791486
  34. RAIDD is a new 'death' adaptor molecule.
    Nature. 1997 Jan 2;385(6611):86-9 PMID: 8985253
  35. 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 U S A. 1997 Jan 21;94(2):690-4 PMID: 9012846
  36. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis.
    Science. 1997 Feb 14;275(5302):983-6 PMID: 9020082
  37. Interaction between the C. elegans cell-death regulators CED-9 and CED-4.
    Nature. 1997 Feb 13;385(6617):653-6 PMID: 9024666
  38. Bcl-2, Bcl-XL and adenovirus protein E1B19kD are functionally equivalent in their ability to inhibit cell death.
    Oncogene. 1997 Jan 30;14(4):405-14 PMID: 9053837
  39. Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death.
    Science. 1997 Feb 21;275(5303):1122-6 PMID: 9027312
  40. Interaction and regulation of subcellular localization of CED-4 by CED-9.
    Science. 1997 Feb 21;275(5303):1126-9 PMID: 9027313
  41. Controlling cell death.
    Science. 1997 Feb 21;275(5303):1081-2 PMID: 9054009
  42. The proto-oncogene Bcl-2 and its role in regulating apoptosis.
    Nat Med. 1997 Jun;3(6):614-20 PMID: 9176486
  43. Interaction and regulation of the Caenorhabditis elegans death protease CED-3 by CED-4 and CED-9.
    J Biol Chem. 1997 Aug 22;272(34):21449-54 PMID: 9261161
  44. Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3.
    Cell. 1997 Aug 8;90(3):405-13 PMID: 9267021
  45. Caspases: the executioners of apoptosis.
    Biochem J. 1997 Aug 15;326 ( Pt 1):1-16 PMID: 9337844
  46. Apoptosis-associated signaling pathways are required for chemotherapy-mediated female germ cell destruction.
    Nat Med. 1997 Nov;3(11):1228-32 PMID: 9359697
  47. Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12401-6 PMID: 9356461
  48. The bcl-2 family of proteins.
    Br Med Bull. 1997;53(3):466-77 PMID: 9374031
  49. Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins.
    J Biol Chem. 1997 Dec 5;272(49):30866-72 PMID: 9388232
  50. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.
    Cell. 1997 Nov 14;91(4):479-89 PMID: 9390557
  51. Apoptosis and ovarian function.
    Rev Reprod. 1996 Sep;1(3):162-72 PMID: 9414454
  52. Bim: a novel member of the Bcl-2 family that promotes apoptosis.
    EMBO J. 1998 Jan 15;17(2):384-95 PMID: 9430630
  53. A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions.
    EMBO J. 1995 Nov 15;14(22):5589-96 PMID: 8521816
  54. Life, death, and the pursuit of apoptosis.
    Genes Dev. 1996 Jan 1;10(1):1-15 PMID: 8557188
  55. Bax-independent inhibition of apoptosis by Bcl-XL.
    Nature. 1996 Feb 8;379(6565):554-6 PMID: 8596636
  56. Developing Caenorhabditis elegans neurons may contain both cell-death protective and killer activities.
    Genes Dev. 1996 Mar 1;10(5):578-91 PMID: 8598288
  57. Proapoptotic protein Bax heterodimerizes with Bcl-2 and homodimerizes with Bax via a novel domain (BH3) distinct from BH1 and BH2.
    J Biol Chem. 1996 Mar 29;271(13):7440-4 PMID: 8631771
  58. ICE family proteases: mediators of all apoptotic cell death?
    Immunity. 1996 Mar;4(3):195-201 PMID: 8624810
  59. Molecular ordering of the cell death pathway. Bcl-2 and Bcl-xL function upstream of the CED-3-like apoptotic proteases.
    J Biol Chem. 1996 Mar 1;271(9):4573-6 PMID: 8617712
  60. Inhibition of testicular germ cell apoptosis and differentiation in mice misexpressing Bcl-2 in spermatogonia.
    Development. 1996 Jun;122(6):1703-9 PMID: 8674410
  61. ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease granzyme B.
    J Biol Chem. 1996 Jul 12;271(28):16720-4 PMID: 8663294
  62. Fas-induced activation of the cell death-related protease CPP32 Is inhibited by Bcl-2 and by ICE family protease inhibitors.
    J Biol Chem. 1996 Jul 12;271(28):16850-5 PMID: 8663439
  63. An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor.
    Cell. 1996 Jul 26;86(2):201-8 PMID: 8706125
  64. bcl-w, a novel member of the bcl-2 family, promotes cell survival.
    Oncogene. 1996 Aug 15;13(4):665-75 PMID: 8761287
  65. Bax can antagonize Bcl-XL during etoposide and cisplatin-induced cell death independently of its heterodimerization with Bcl-XL.
    J Biol Chem. 1996 Sep 13;271(37):22764-72 PMID: 8798452
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.1.167
Published
1999-01-04
Pages
167-78
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171112
Subset
IM
Grants
NIEHS NIH HHS · ES08111 · United States
Databases
GENBANK
AF102501
External Links
PubMed source DOI: 10.1093/emboj/18.1.167 PMC Full Text View journal details
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