PMID- 10617621
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 1
DP  - 2000 Jan 7
TI  - Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in
      response to DNA damage.
PG  - 322-7
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.
FAU - Kharbanda, S
AU  - Kharbanda S
AD  - Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical
      School, Boston, Massachusetts 02115, USA. surendervkharbanda@dfci.harvard.edu
FAU - Saxena, S
AU  - Saxena S
FAU - Yoshida, K
AU  - Yoshida K
FAU - Pandey, P
AU  - Pandey P
FAU - Kaneki, M
AU  - Kaneki M
FAU - Wang, Q
AU  - Wang Q
FAU - Cheng, K
AU  - Cheng K
FAU - Chen, Y N
AU  - Chen YN
FAU - Campbell, A
AU  - Campbell A
FAU - Sudha, T
AU  - Sudha T
FAU - Yuan, Z M
AU  - Yuan ZM
FAU - Narula, J
AU  - Narula J
FAU - Weichselbaum, R
AU  - Weichselbaum R
FAU - Nalin, C
AU  - Nalin C
FAU - Kufe, D
AU  - Kufe D
LA  - eng
GR  - CA 55421/CA/NCI NIH HHS/United States
GR  - CA 75216/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (BCL2L1 protein, human)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Recombinant Proteins)
RN  - 0 (bcl-X Protein)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
EIN - J Biol Chem 2000 Jun 23;275(25):19433
MH  - Apoptosis/*physiology
MH  - Biological Transport
MH  - Cell Compartmentation
MH  - DNA Damage/*physiology
MH  - Humans
MH  - Mitochondria/*metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Mutagenesis
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism
MH  - Radiation, Ionizing
MH  - Recombinant Proteins/metabolism
MH  - U937 Cells
MH  - bcl-X Protein
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - 10.1074/jbc.275.1.322 [doi]
AID - S0021-9258(19)52868-X [pii]
PST - ppublish
SO  - J Biol Chem. 2000 Jan 7;275(1):322-7. doi: 10.1074/jbc.275.1.322.