Cell Cycle Arrest and Apoptosis Induction by Activator Protein 2\alpha (AP-2\alpha) and the Role of $p53$ and $p21^{WAF1/CIP1}$ in AP-2\alpha-mediated Growth Inhibition

Wajapeyee, Narendra and Somasundaram, Kumaravel (2003) Cell Cycle Arrest and Apoptosis Induction by Activator Protein 2\alpha (AP-2\alpha) and the Role of $p53$ and $p21^{WAF1/CIP1}$ in AP-2\alpha-mediated Growth Inhibition. In: The Journal of Biological Chemistry, 278 (52). pp. 52093-52101.

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Abstract

Activator protein 2\alpha (AP-2\alpha) is a sequence-specific DNA-binding transcription factor implicated in differentiation and transformation. In this study, we have made a replication-deficient recombinant adenovirus that expresses functional AP-2\alpha(Ad-AP2). Cells infected with Ad-AP2 expressed induced levels of AP-2\alpha protein, which bound to DNA in a sequence-specific manner and activated the AP-2-specific reporter 3X-AP2. Expression of AP-2\alpha from Ad-AP2 inhibited cellular DNA synthesis and induced apoptosis. Ad-AP2 infection resulted in efficient inhibition of growth of cancer cells of six different types. In addition, prior expression of AP-2\alpha increased the chemosensitivity of H460, a lung carcinoma cell line, to adriamycin (2.5-fold) and cisplatin (5-fold). Furthermore, the growth inhibition by AP-2\alpha was found to be less efficient in the absence of p53 or p21, which correlated with reduced apoptosis in p53 null cells and lack of DNA synthesis inhibition in $p21^{WAF1/CIP1}$ null cells by AP-2\alpha, respectively. These results suggest that AP-2\alpha inhibits the growth of cells by inducing cell cycle arrest and apoptosis and that the use of AP-2\alpha should be explored as a therapeutic strategy either alone or in combination with chemotherapy.

Item Type:	Journal Article
Publication:	The Journal of Biological Chemistry
Publisher:	American Society for Biochemistry and Molecular Biology
Additional Information:	The Copyright belongs to American Society for Biochemistry and Molecular Biology.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	19 Apr 2006
Last Modified:	19 Sep 2010 04:25
URI:	http://eprints.iisc.ac.in/id/eprint/6320

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