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 journalArticlepeer-review

392 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 languageEnglish
Pages (from-to)322-327
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number1
DOIs
StatePublished - 7 Jan 2000
Externally publishedYes

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