Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage

Surender Kharbanda; Satya Saxena; Kiyotsugu Yoshida; Pramod Pandey; Masao Kaneki; Qizhi Wang; Keding Cheng; Ying Nan Chen; Angela Campbell; Thangrila Sudha; Zhi Min Yuan; Jagat Narula; Ralph Weichselbaum; Carlo Nalin; Donald Kufe

doi:10.1074/jbc.275.1.322

Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage

Surender Kharbanda, Satya Saxena, Kiyotsugu Yoshida, Pramod Pandey, Masao Kaneki, Qizhi Wang, Keding Cheng, Ying Nan Chen, Angela Campbell, Thangrila Sudha, Zhi Min Yuan, Jagat Narula, Ralph Weichselbaum, Carlo Nalin, Donald Kufe

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

400 Scopus citations

Abstract

Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic agents is necessary for induction of apoptosis. We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mitochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (Thr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant Bcl-x(L) with the two threonines substituted by alanines (Ala-47, Ala- 115) is a more potent inhibitor of ionizing radiation-induced apoptosis. These findings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genotoxic stress.

Original language	English
Pages (from-to)	322-327
Number of pages	6
Journal	Journal of Biological Chemistry
Volume	275
Issue number	1
DOIs	https://doi.org/10.1074/jbc.275.1.322
State	Published - 7 Jan 2000
Externally published	Yes

Access to Document

10.1074/jbc.275.1.322

Cite this

Kharbanda, S., Saxena, S., Yoshida, K., Pandey, P., Kaneki, M., Wang, Q., Cheng, K., Chen, Y. N., Campbell, A., Sudha, T., Yuan, Z. M., Narula, J., Weichselbaum, R., Nalin, C., & Kufe, D. (2000). Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage. Journal of Biological Chemistry, 275(1), 322-327. https://doi.org/10.1074/jbc.275.1.322

@article{ea9c786d7bb346dfb57f0c0a90fca22c,

title = "Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage",

abstract = "Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic agents is necessary for induction of apoptosis. We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mitochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (Thr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant Bcl-x(L) with the two threonines substituted by alanines (Ala-47, Ala- 115) is a more potent inhibitor of ionizing radiation-induced apoptosis. These findings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genotoxic stress.",

author = "Surender Kharbanda and Satya Saxena and Kiyotsugu Yoshida and Pramod Pandey and Masao Kaneki and Qizhi Wang and Keding Cheng and Chen, {Ying Nan} and Angela Campbell and Thangrila Sudha and Yuan, {Zhi Min} and Jagat Narula and Ralph Weichselbaum and Carlo Nalin and Donald Kufe",

year = "2000",

month = jan,

day = "7",

doi = "10.1074/jbc.275.1.322",

language = "English",

volume = "275",

pages = "322--327",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology Inc.",

number = "1",

}

Kharbanda, S, Saxena, S, Yoshida, K, Pandey, P, Kaneki, M, Wang, Q, Cheng, K, Chen, YN, Campbell, A, Sudha, T, Yuan, ZM, Narula, J, Weichselbaum, R, Nalin, C & Kufe, D 2000, 'Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage', Journal of Biological Chemistry, vol. 275, no. 1, pp. 322-327. https://doi.org/10.1074/jbc.275.1.322

TY - JOUR

T1 - Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage

AU - Kharbanda, Surender

AU - Saxena, Satya

AU - Yoshida, Kiyotsugu

AU - Pandey, Pramod

AU - Kaneki, Masao

AU - Wang, Qizhi

AU - Cheng, Keding

AU - Chen, Ying Nan

AU - Campbell, Angela

AU - Sudha, Thangrila

AU - Yuan, Zhi Min

AU - Narula, Jagat

AU - Weichselbaum, Ralph

AU - Nalin, Carlo

AU - Kufe, Donald

PY - 2000/1/7

Y1 - 2000/1/7

N2 - Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic agents is necessary for induction of apoptosis. We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mitochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (Thr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant Bcl-x(L) with the two threonines substituted by alanines (Ala-47, Ala- 115) is a more potent inhibitor of ionizing radiation-induced apoptosis. These findings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genotoxic stress.

AB - Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic agents is necessary for induction of apoptosis. We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mitochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (Thr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant Bcl-x(L) with the two threonines substituted by alanines (Ala-47, Ala- 115) is a more potent inhibitor of ionizing radiation-induced apoptosis. These findings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genotoxic stress.

UR - http://www.scopus.com/inward/record.url?scp=0034614658&partnerID=8YFLogxK

U2 - 10.1074/jbc.275.1.322

DO - 10.1074/jbc.275.1.322

M3 - Article

C2 - 10617621

AN - SCOPUS:0034614658

SN - 0021-9258

VL - 275

SP - 322

EP - 327

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 1

ER -

Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage

Abstract

Access to Document

Fingerprint

Cite this