Home LiteratureArticle Details
PMID: 15136728 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 20 ·2004-05-18 ·Pages 7681-6

Zhu Y, Swanson BJ, Wang M, Hildeman DA, Schaefer BC, Liu X, Suzuki H, Mihara K, Kappler J, Marrack P

Abstract

Apoptosis in activated T cells in vivo requires the proapoptotic Bcl-2 family member Bim. We show here that, despite its ability to bind LC8, a component of the microtubule dynein motor complex, most of the Bim in both healthy and apoptotic T cells is associated with mitochondria, not microtubules. In healthy resting T cells Bim is bound to the antiapoptotic proteins Bcl-2 and Bcl-x(L). In activated T cells, levels of Bcl-2 fall, and Bim is associated more with Bcl-x(L) and less with Bcl-2. Our results indicate that, in T cells, Bim function is regulated by interaction with Bcl-2 family members on mitochondria rather than by sequestration to the microtubules.

MeSH Terms
Animals Apoptosis/physiology Cell Membrane/metabolism Fluorescent Antibody Technique Mice Mitochondria/metabolism Mutation Proto-Oncogene Proteins c-bcl-2/genetics,metabolism T-Lymphocytes/metabolism
Chemicals
Proto-Oncogene Proteins c-bcl-2
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Zhu Yanan
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Swanson Bradley J
Wang Michael
Hildeman David A
Schaefer Brian C
Liu Xinqi
Suzuki Hiroyuki
Mihara Katsuyoshi
Kappler John
Marrack Philippa
References (45)
45 references, click to expand
  1. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis.
    Science. 1997 Feb 14;275(5302):983-6 PMID: 9020082
  2. The pCL vector system: rapid production of helper-free, high-titer, recombinant retroviruses.
    J Virol. 1996 Aug;70(8):5701-5 PMID: 8764092
  3. Cutting edge: increased expression of Bcl-2 in antigen-specific memory CD8+ T cells.
    J Immunol. 2000 Apr 15;164(8):3950-4 PMID: 10754284
  4. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c.
    Genes Dev. 2000 Aug 15;14(16):2060-71 PMID: 10950869
  5. Characterization of the signal that directs Tom20 to the mitochondrial outer membrane.
    J Cell Biol. 2000 Oct 16;151(2):277-88 PMID: 11038175
  6. Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1.
    Curr Biol. 2000 Oct 5;10(19):1201-4 PMID: 11050388
  7. Characterization of rat TOM40, a central component of the preprotein translocase of the mitochondrial outer membrane.
    J Biol Chem. 2000 Dec 1;275(48):37930-6 PMID: 10980201
  8. Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis.
    Neuron. 2001 Mar;29(3):615-28 PMID: 11301022
  9. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death.
    Science. 2001 Apr 27;292(5517):727-30 PMID: 11326099
  10. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak.
    Genes Dev. 2001 Jun 15;15(12):1481-6 PMID: 11410528
  11. Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes.
    J Clin Invest. 2001 Sep;108(6):871-8 PMID: 11560956
  12. A novel family of retroviral vectors for the rapid production of complex stable cell lines.
    Anal Biochem. 2001 Oct 1;297(1):86-93 PMID: 11567531
  13. Voltage-dependent anion-selective channel (VDAC) interacts with the dynein light chain Tctex1 and the heat-shock protein PBP74.
    Int J Biochem Cell Biol. 2002 Sep;34(9):1059-70 PMID: 12009301
  14. Gephyrin interacts with Dynein light chains 1 and 2, components of motor protein complexes.
    J Neurosci. 2002 Jul 1;22(13):5393-402 PMID: 12097491
  15. Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim.
    Immunity. 2002 Jun;16(6):759-67 PMID: 12121658
  16. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics.
    Cancer Cell. 2002 Sep;2(3):183-92 PMID: 12242151
  17. Bcl-2 and porin follow different pathways of TOM-dependent insertion into the mitochondrial outer membrane.
    J Mol Biol. 2002 Nov 1;323(4):729-38 PMID: 12419260
  18. Characterization of the signal that directs Bcl-x(L), but not Bcl-2, to the mitochondrial outer membrane.
    J Cell Biol. 2003 Jan 6;160(1):53-64 PMID: 12515824
  19. The N-terminal end of Bax contains a mitochondrial-targeting signal.
    J Biol Chem. 2003 Mar 28;278(13):11633-41 PMID: 12529375
  20. Activation-induced cell death in T cells.
    Immunol Rev. 2003 Jun;193:70-81 PMID: 12752672
  21. The interaction of peripheral proteins and membranes studied with alpha-lactalbumin and phospholipid bilayers of various compositions.
    J Biol Chem. 2003 Jun 13;278(24):21790-7 PMID: 12660251
  22. The structure of a Bcl-xL/Bim fragment complex: implications for Bim function.
    Immunity. 2003 Sep;19(3):341-52 PMID: 14499110
  23. Caspase cleavage of BimEL triggers a positive feedback amplification of apoptotic signaling.
    Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1235-40 PMID: 14732682
  24. Regulation of expression of Bcl-2 protein family member Bim by T cell receptor triggering.
    Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3011-6 PMID: 14970329
  25. A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids.
    Anal Biochem. 1984 Apr;138(1):141-3 PMID: 6731838
  26. Isotypic exclusion of gamma delta T cell receptors in transgenic mice bearing a rearranged beta-chain gene.
    Science. 1988 Aug 26;241(4869):1089-92 PMID: 2970670
  27. The distribution, abundance and subcellular localization of kinesin.
    J Cell Biol. 1989 Jun;108(6):2335-42 PMID: 2525563
  28. Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen.
    Nature. 1989 Nov 30;342(6249):559-61 PMID: 2573841
  29. The transport and binding of taxol.
    Gen Pharmacol. 1997 Aug;29(2):167-72 PMID: 9251895
  30. Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL.
    Mol Cell Biol. 1997 Dec;17(12):7040-6 PMID: 9372935
  31. Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria.
    Cell. 1997 Nov 28;91(5):627-37 PMID: 9393856
  32. Bim: a novel member of the Bcl-2 family that promotes apoptosis.
    EMBO J. 1998 Jan 15;17(2):384-95 PMID: 9430630
  33. Bax in murine thymus is a soluble monomeric protein that displays differential detergent-induced conformations.
    J Biol Chem. 1998 Apr 24;273(17):10777-83 PMID: 9553144
  34. Improved green fluorescent protein by molecular evolution using DNA shuffling.
    Nat Biotechnol. 1996 Mar;14(3):315-9 PMID: 9630892
  35. Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis.
    EMBO J. 1998 Jul 15;17(14):3878-85 PMID: 9670005
  36. Rapid hybridoma screening method for the identification of monoclonal antibodies to low-abundance cytoplasmic proteins.
    Biotechniques. 1998 Nov;25(5):824-30 PMID: 9821584
  37. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex.
    Mol Cell. 1999 Mar;3(3):287-96 PMID: 10198631
  38. Bystander virus infection prolongs activated T cell survival.
    J Immunol. 1999 Apr 15;162(8):4527-35 PMID: 10201991
  39. The membrane association domain of RGS16 contains unique amphipathic features that are conserved in RGS4 and RGS5.
    J Biol Chem. 1999 Jul 9;274(28):19799-806 PMID: 10391923
  40. Reactive oxygen species regulate activation-induced T cell apoptosis.
    Immunity. 1999 Jun;10(6):735-44 PMID: 10403648
  41. Amphitropic proteins: regulation by reversible membrane interactions (review).
    Mol Membr Biol. 1999 Jul-Sep;16(3):217-35 PMID: 10503244
  42. Interaction of peptides corresponding to mitochondrial presequences with membranes.
    J Biol Chem. 1991 Nov 15;266(32):21693-9 PMID: 1834660
  43. Activation-induced death of mature T cells in the regulation of immune responses.
    Curr Opin Immunol. 1995 Jun;7(3):382-8 PMID: 7546404
  44. Transfecting mammalian cells: optimization of critical parameters affecting calcium-phosphate precipitate formation.
    Nucleic Acids Res. 1996 Feb 15;24(4):596-601 PMID: 8604299
  45. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity.
    Science. 1999 Nov 26;286(5445):1735-8 PMID: 10576740
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0402293101
Published
2004-05-18
Epub
2004-00-10
Pages
7681-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC419666
Subset
IM
Grants
NIAID NIH HHS · AI-52225 · United States
NIAID NIH HHS · R01 AI018785 · United States
NIAID NIH HHS · R01 AI052225 · United States
NIAID NIH HHS · AI-17134 · United States
NIAID NIH HHS · AI-18785 · United States
NICHD NIH HHS · K12 HD000850 · United States
NIAID NIH HHS · R01 AI017134 · United States
NICHD NIH HHS · K12-HD00850-17 · United States
NIAID NIH HHS · R37 AI018785 · United States
NIAID NIH HHS · R56 AI017134 · United States
NIAID NIH HHS · AI-22295 · United States
NIAID NIH HHS · R56 AI018785 · United States
NIAID NIH HHS · P01 AI022295 · United States
External Links
PubMed source DOI: 10.1073/pnas.0402293101 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2