HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 24, 25313-25319, June 11, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/24/25313    most recent M400932200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kalra, N. Articles by Kumar, V. Search for Related Content PubMed PubMed Citation Articles by Kalra, N. Articles by Kumar, V. Social Bookmarking                      What's this?

c-Fos Is a Mediator of the c-Myc-induced Apoptotic Signaling in Serum-deprived Hepatoma Cells via the p38 Mitogen-activated Protein Kinase Pathway^*

Neetu Kalra and Vijay Kumar

From the Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India

The proto-oncogene c-myc encodes a transcription factor that plays a pivotal role in cell proliferation, differentiation, and apoptosis. The signaling mechanism of c-Myc-induced apoptosis was investigated on the human hepatoma Huh7 cells under growth factor-deprived conditions. The apoptotic process did not involve p53. Rather it was dependent on the expression of c-Fos. Activation of caspases 3 and 9 and down-regulation of Bcl2 were observed in the apoptotic process, indicating it to be a mitochondria-dependent event. An increase in the p38 mitogen-activated protein kinase that was mediated by a Rac1-dependent and cdc42-independent pathway eventually leading to up-regulation of c-Fos activity was also observed. Deletion analysis of the promoter region of the c-fos gene indicated that the ATF2-responsive element conferred the Myc-induced expression of c-Fos. Co-expression of the dominant-negative mutants of c-Fos, p38, and Rac1 blocked the Myc-mediated apoptosis. SB20358, a chemical inhibitor of p38 pathway, also specifically blocked the apoptotic signaling by c-Myc. Furthermore, co-expression of the hepatitis B virus X protein (HBx) along with Myc abrogated the apoptotic signals. The HBx expression was associated with an increase in the levels of phosphorylated AKT and down-regulation of c-Fos by Myc. Thus, c-Fos seems be a new mediator of c-Myc-induced apoptosis.

Received for publication, January 28, 2004 , and in revised form, March 29, 2004.

^* This work was supported by core grants from the International Centre for Genetic Engineering and Biotechnology, New Delhi. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of Senior Research Fellowship from the Council of Scientific and Industrial Research, New Delhi.

To whom correspondence should be addressed: I.C.G.E.B., P.O. Box 10504, Aruna Asaf Ali Marg, New Delhi 110067, India. Tel.: 91-11-26176680; Fax: 91-11-26162316; E-mail: vijay{at}icgeb.res.in.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Morgan, P. M. Pirard, L. Shears, J. Sohal, R. Pettengell, and H. S. Pandha Antagonism of HOX/PBX Dimer Formation Blocks the In vivo Proliferation of Melanoma Cancer Res., June 15, 2007; 67(12): 5806 - 5813. [Abstract] [Full Text] [PDF]

				S. Jin, R. M. Ray, and L. R. Johnson Rac1 mediates intestinal epithelial cell apoptosis via JNK Am J Physiol Gastrointest Liver Physiol, December 1, 2006; 291(6): G1137 - G1147. [Abstract] [Full Text] [PDF]

				M. Surjit, B. Liu, V. T. K. Chow, and S. K. Lal The Nucleocapsid Protein of Severe Acute Respiratory Syndrome-Coronavirus Inhibits the Activity of Cyclin-Cyclin-dependent Kinase Complex and Blocks S Phase Progression in Mammalian Cells J. Biol. Chem., April 21, 2006; 281(16): 10669 - 10681. [Abstract] [Full Text] [PDF]

				T. Tanos, M. J. Marinissen, F. C. Leskow, D. Hochbaum, H. Martinetto, J. S. Gutkind, and O. A. Coso Phosphorylation of c-Fos by Members of the p38 MAPK Family: ROLE IN THE AP-1 RESPONSE TO UV LIGHT J. Biol. Chem., May 13, 2005; 280(19): 18842 - 18852. [Abstract] [Full Text] [PDF]

				J. Hess, P. Angel, and M. Schorpp-Kistner AP-1 subunits: quarrel and harmony among siblings J. Cell Sci., December 1, 2004; 117(25): 5965 - 5973. [Abstract] [Full Text] [PDF]