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PMID: 12223490 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress.

The Journal of biological chemistry ·Vol. 277 ·No. 46 ·2002-11-15 ·Pages 43730-4

Inoshita S, Takeda K, Hatai T, Terada Y, Sano M, Hata J, Umezawa A, Ichijo H

Abstract

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.

MeSH Terms

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 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 p38 Mitogen-Activated Protein Kinases

Chemicals

DNA, Complementary Mcl1 protein, mouse Myeloid Cell Leukemia Sequence 1 Protein Neoplasm Proteins Proto-Oncogene Proteins c-bcl-2 Threonine Serine Hydrogen Peroxide Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases Phosphoric Monoester Hydrolases Alanine Oxygen

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Inoshita Seiji

Laboratory of Cell Signaling, Department of Hard Tissue Engineering, Division of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.

Takeda Kohsuke

Hatai Takiko

Terada Yoshio

Sano Makoto

Hata Junichi

Umezawa Akihiro

Ichijo Hidenori

Article Info

Journal

The Journal of biological chemistry

Abbr.

J Biol Chem

ISSN

0021-9258

DOI

10.1074/jbc.M207951200

Published

2002-11-15

Epub

2002-00-09

Pages

43730-4

Language

English

Region

United States

NLM ID

2985121R

Subset

External Links

PubMed source DOI: 10.1074/jbc.M207951200 View journal details

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Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress.

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