Phosphorylation and Inactivation of Myeloid Cell Leukemia 1 by JNK in Response to Oxidative Stress

Oxidative stress induces JNK activation, which leads to apoptosis through mitochondria-dependent caspase activation. However, little is known about the mechanism by which JNK alters mitochondrial function. In this study, we investigated the role of phosphorylation of myeloid cell leukemia 1 (Mcl-1),...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-11, Vol.277 (46), p.43730-43734
Main Authors: Inoshita, Seiji, Takeda, Kohsuke, Hatai, Takiko, Terada, Yoshio, Sano, Makoto, Hata, Junichi, Umezawa, Akihiro, Ichijo, Hidenori
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Alanine - metabolism
Amino Acid Sequence
Animals
Apoptosis
Binding Sites
Blotting, Western
Cell Line
Cell Survival
DNA, Complementary - metabolism
Escherichia coli - metabolism
Humans
Hydrogen Peroxide - pharmacology
Mice
Mitochondria - metabolism
Mitogen-Activated Protein Kinase 8
Mitogen-Activated Protein Kinases - metabolism
Molecular Sequence Data
Myeloid Cell Leukemia Sequence 1 Protein
Neoplasm Proteins - metabolism
Oxidative Stress
Oxygen - metabolism
p38 Mitogen-Activated Protein Kinases
Phosphoric Monoester Hydrolases - metabolism
Phosphorylation
Plasmids - metabolism
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Proteins c-bcl-2
Sequence Homology, Amino Acid
Serine - metabolism
Threonine - metabolism
Transfection
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Summary:Oxidative stress induces JNK activation, which leads to apoptosis through mitochondria-dependent caspase activation. However, little is known about the mechanism by which JNK alters mitochondrial function. In this study, we investigated the role of phosphorylation of myeloid cell leukemia 1 (Mcl-1), an anti-apoptotic member of the Bcl-2 family, in oxidative stress-induced apoptosis. We found that JNK phosphorylated Ser-121 and Thr-163 of Mcl-1 in response to stimulation with H 2 O 2 and that transfection of unphosphorylatable Mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with H 2 O 2 . JNK-dependent phosphorylation and thus inactivation of Mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M207951200