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

Yanan Zhu; Bradley J. Swanson; Michael Wang; David A. Hildeman; Brian C. Schaefer; Xinqi Liu; Hiroyuki Suzuki; Katsuyoshi Mihara; John Kappler; Philippa Marrack

doi:10.1073/pnas.0402293101

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

Yanan Zhu, Bradley J. Swanson, Michael Wang, David A. Hildeman, Brian C. Schaefer, Xinqi Liu, Hiroyuki Suzuki, Katsuyoshi Mihara, John Kappler, Philippa Marrack^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

113 Scopus citations

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.

Original language	English
Pages (from-to)	7681-7686
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	101
Issue number	20
DOIs	https://doi.org/10.1073/pnas.0402293101
State	Published - 18 May 2004
Externally published	Yes

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10.1073/pnas.0402293101

Cite this

Zhu, Y., Swanson, B. J., Wang, M., Hildeman, D. A., Schaefer, B. C., Liu, X., Suzuki, H., Mihara, K., Kappler, J., & Marrack, P. (2004). 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, 101(20), 7681-7686. https://doi.org/10.1073/pnas.0402293101

@article{da69218dc04847a595701b91895bff3b,

title = "Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells",

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-xL. In activated T cells, levels of Bcl-2 fall, and Bim is associated more with Bcl-xL 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.",

author = "Yanan Zhu and Swanson, {Bradley J.} and Michael Wang and Hildeman, {David A.} and Schaefer, {Brian C.} and Xinqi Liu and Hiroyuki Suzuki and Katsuyoshi Mihara and John Kappler and Philippa Marrack",

year = "2004",

month = may,

day = "18",

doi = "10.1073/pnas.0402293101",

language = "English",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Zhu, Y, Swanson, BJ, Wang, M, Hildeman, DA, Schaefer, BC, Liu, X, Suzuki, H, Mihara, K, Kappler, J & Marrack, P 2004, '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, pp. 7681-7686. https://doi.org/10.1073/pnas.0402293101

TY - JOUR

T1 - Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells

AU - Zhu, Yanan

AU - Swanson, Bradley J.

AU - Wang, Michael

AU - Hildeman, David A.

AU - Schaefer, Brian C.

AU - Liu, Xinqi

AU - Suzuki, Hiroyuki

AU - Mihara, Katsuyoshi

AU - Kappler, John

AU - Marrack, Philippa

PY - 2004/5/18

Y1 - 2004/5/18

N2 - 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-xL. In activated T cells, levels of Bcl-2 fall, and Bim is associated more with Bcl-xL 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.

AB - 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-xL. In activated T cells, levels of Bcl-2 fall, and Bim is associated more with Bcl-xL 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.

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U2 - 10.1073/pnas.0402293101

DO - 10.1073/pnas.0402293101

M3 - Article

C2 - 15136728

AN - SCOPUS:2442656629

SN - 0027-8424

VL - 101

SP - 7681

EP - 7686

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 20

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