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.
authors.affiliation: Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. surendervkharbanda@dfci.harvard.edu
authors.forename: S
authors.initials: S
authors.lastname: Kharbanda
authors.forename: S
authors.initials: S
authors.lastname: Saxena
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: P
authors.initials: P
authors.lastname: Pandey
authors.forename: M
authors.initials: M
authors.lastname: Kaneki
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Cheng
authors.forename: Y N
authors.initials: YN
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Campbell
authors.forename: T
authors.initials: T
authors.lastname: Sudha
authors.forename: Z M
authors.initials: ZM
authors.lastname: Yuan
authors.forename: J
authors.initials: J
authors.lastname: Narula
authors.forename: R
authors.initials: R
authors.lastname: Weichselbaum
authors.forename: C
authors.initials: C
authors.lastname: Nalin
authors.forename: D
authors.initials: D
authors.lastname: Kufe
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001692:Biological Transport; D002451:Cell Compartmentation; D004249:DNA Damage / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016296:Mutagenesis; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D011994:Recombinant Proteins / Q000378:metabolism; D020298:U937 Cells; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051020:bcl-X Protein; D020928:Mitogen-Activated Protein Kinases