Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Cell Biol. 175 (4): 607-617

Copyright © 2006 by the Rockefeller University Press.


Article

IKKß programs to turn on the GADD45{alpha}–MKK4–JNK apoptotic cascade specifically via p50 NF-{kappa}B in arsenite response

Lun Song1, Jingxia Li1, Dongyun Zhang1, Zheng-gang Liu2, Jianping Ye3, Qimin Zhan4, Han-Ming Shen5, Matt Whiteman6, , and Chuanshu Huang1

1 Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987
2 Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
3 Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808
4 National Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, 100021, People's Republic of China
5 Department of Community, Occupational, and Family Medicine and 6 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore 117597, Singapore

Correspondence to Chuanshu Huang: chuanshu{at}env.med.nyu.edu

Abstract: Cross talk between NF-{kappa}B and c-Jun N-terminal kinases (JNKs) has been implicated in the cell life and death decision under various stresses. Functional suppression of JNK activation by NF-{kappa}B has recently been proposed as a key cellular survival mechanism and contributes to cancer cells escaping from apoptosis. We provide a novel scenario of the proapoptotic role of I{kappa}B kinase ß (IKKß)–NF-{kappa}B, which can act as the activator of the JNK pathway through the induction of GADD45{alpha} for triggering MKK4/JNK activation, in response to the stimulation of arsenite, a cancer therapeutic reagent. This effect of IKKß–NF-{kappa}B is dependent on p50 but not the p65/relA NF-{kappa}B subunit, which can increase the stability of GADD45{alpha} protein through suppressing its ubiquitination and proteasome-dependent degradation. IKKß–NF-{kappa}B can therefore either activate or suppress the JNK cascade and consequently mediate pro- or antiapoptotic effects, depending on the manner of its induction. Furthermore, the NF-{kappa}B p50 subunit can exert a novel regulatory function on protein modification independent of the classical NF-{kappa}B transcriptional activity.

Abbreviations used in this paper: CHX, cyclohexamide; GADD, growth arrest and DNA damage inducible; IKK, I{kappa}B kinase; MEF, mouse embryonic fibroblast; PARP, poly (ADP-ribose) polymerase; WT, wild-type.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
NF{kappa}B1 (p50) suppresses SOD2 expression by inhibiting FoxO3a transactivation in a miR190/PHLPP1/Akt-dependent axis.
K. Du, Y. Yu, D. Zhang, W. Luo, H. Huang, J. Chen, J. Gao, and C. Huang (2013)
Mol. Biol. Cell 24, 3577-3583
   Abstract »    Full Text »    PDF »
Cyclin D1 Downregulation Contributes to Anticancer Effect of Isorhapontigenin on Human Bladder Cancer Cells.
Y. Fang, Z. Cao, Q. Hou, C. Ma, C. Yao, J. Li, X.-R. Wu, and C. Huang (2013)
Mol. Cancer Ther. 12, 1492-1503
   Abstract »    Full Text »    PDF »
X-linked Inhibitor of Apoptosis Protein (XIAP) Regulation of Cyclin D1 Protein Expression and Cancer Cell Anchorage-independent Growth via Its E3 Ligase-mediated Protein Phosphatase 2A/c-Jun Axis.
Z. Cao, R. Zhang, J. Li, H. Huang, D. Zhang, J. Zhang, J. Gao, J. Chen, and C. Huang (2013)
J. Biol. Chem. 288, 20238-20247
   Abstract »    Full Text »    PDF »
Ribosomal protein S7 regulates arsenite-induced GADD45{alpha} expression by attenuating MDM2-mediated GADD45{alpha} ubiquitination and degradation.
M. Gao, X. Li, W. Dong, R. Jin, H. Ma, P. Yang, M. Hu, Y. Li, Y. Hao, S. Yuan, et al. (2013)
Nucleic Acids Res. 41, 5210-5222
   Abstract »    Full Text »    PDF »
Expression of NFkB1, GADD45A and JNK1 in Salivary Gland Carcinomas of Different Histotypes.
G. GOBEL, I. SZANYI, P. REVESZ, M. BAUER, I. GERLINGER, A. NEMETH, I. EMBER, K. GOCZE, and K. GOMBOS (2013)
Cancer Genomics Proteomics 10, 81-87
   Abstract »    Full Text »    PDF »
Effects of Purified Glycerol from Biodiesel on miRNAs Compared to the Expression Profile of Selected mRNAs in Balb/c Mice.
E. SZELE, K. GOMBOS, K. JUHASZ, V. WOHLER, A. KOVACS, and I. EMBER (2013)
In Vivo 27, 107-111
   Abstract »    Full Text »    PDF »
RhoGDI SUMOylation at Lys-138 Increases Its Binding Activity to Rho GTPase and Its Inhibiting Cancer Cell Motility.
J. Yu, D. Zhang, J. Liu, J. Li, Y. Yu, X.-R. Wu, and C. Huang (2012)
J. Biol. Chem. 287, 13752-13760
   Abstract »    Full Text »    PDF »
IKK{alpha} contributes to UVB-induced VEGF expression by regulating AP-1 transactivation.
W. Dong, Y. Li, M. Gao, M. Hu, X. Li, S. Mai, N. Guo, S. Yuan, and L. Song (2012)
Nucleic Acids Res. 40, 2940-2955
   Abstract »    Full Text »    PDF »
Role of inhibitory {kappa}B kinase and c-Jun NH2-terminal kinase in the development of hepatic insulin resistance in critical illness diabetes.
S. Jiang and J. L. Messina (2011)
Am J Physiol Gastrointest Liver Physiol 301, G454-G463
   Abstract »    Full Text »    PDF »
X-linked Inhibitor of Apoptosis Protein (XIAP) Mediates Cancer Cell Motility via Rho GDP Dissociation Inhibitor (RhoGDI)-dependent Regulation of the Cytoskeleton.
J. Liu, D. Zhang, W. Luo, Y. Yu, J. Yu, J. Li, X. Zhang, B. Zhang, J. Chen, X.-R. Wu, et al. (2011)
J. Biol. Chem. 286, 15630-15640
   Abstract »    Full Text »    PDF »
Effects of Isoflurane on Nf{kappa}b p65, Gadd45a and Jnk1 Expression in the Vital Organs of CBA/CA Mice.
B. KADAR, K. GOMBOS, E. SZELE, I. EMBER, J. L. IVANYI, R. CSEJTEI, and G. PAJKOS (2011)
In Vivo 25, 241-244
   Abstract »    Full Text »    PDF »
p27 Suppresses Arsenite-induced Hsp27/Hsp70 Expression through Inhibiting JNK2/c-Jun- and HSF-1-dependent Pathways.
J. Liu, D. Zhang, X. Mi, Q. Xia, Y. Yu, Z. Zuo, W. Guo, X. Zhao, J. Cao, Q. Yang, et al. (2010)
J. Biol. Chem. 285, 26058-26065
   Abstract »    Full Text »    PDF »
Feeding Purified Glycerol from Biodiesel to CBA/CA Mice: Effects on Gadd45a and Nf{kappa}b1 Expressions.
E. SZELE, K. GOMBOS, A. KOVACS, and I. EMBER (2010)
In Vivo 24, 303-307
   Abstract »    Full Text »    PDF »
A JNK1/AP-1-Dependent, COX-2 Induction Is Implicated in 12-O-Tetradecanoylphorbol-13-Acetate-Induced Cell Transformation through Regulating Cell Cycle Progression.
D. Zhang, J. Li, L. Song, W. Ouyang, J. Gao, and C. Huang (2008)
Mol. Cancer Res. 6, 165-174
   Abstract »    Full Text »    PDF »
A Critical Role for I{kappa}B Kinase beta in Metallothionein-1 Expression and Protection against Arsenic Toxicity.
Z. Peng, L. Peng, Y. Fan, E. Zandi, H. G. Shertzer, and Y. Xia (2007)
J. Biol. Chem. 282, 21487-21496
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882