Journal
EXPERIMENTAL CELL RESEARCH
Volume 312, Issue 8, Pages 1254-1264Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2005.12.013
Keywords
p73; TAp73; Tp73; Delta Np73; Delta TAp73; DeltaNp73; NF kappa B; p53; H1299; Saos-2
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Transactivation domain (TAD)-truncated p73, Delta Np73, associates with p53, resulting in suppression of p53's functions. Using p53 null cell lines, we examined whether or not Delta Np73 can regulate gene expression in a p53-independent manner. When Delta Np73 alpha was cotransfected with a luciferase reporter plasmid with various enhancer elements, NF kappa B-responsive luciferase gene expression was selectively up-regulated by Delta Np73 alpha, but not by other p73-isoforms with TAD and Delta Np73 beta. Deletion of the TAD endowed p73 alpha with the ability to enhance the responsive gene's expression, but deletion of the N-terminal proline-rich domain (PRD) rendered the TAD-deleted p73 alpha inactive. Considering the inability of Delta Np73 beta, which is the C-terminus-truncated form of Delta Np73 alpha, to function, these results indicate that both the PRD and C-terminus are necessary for Delta Np73 alpha to can activate NF kappa B-responsive luciferase expression. Over-expression of p53 suppressed the TAD-truncated p73 alpha-mediated luciferase expression, suggesting that p53 interferes with the TAD-truncated p73 alpha-mediated activation of NF kappa B. Inhibitors for NF kappa B activation reduced the TAD-truncated p73 alpha-dependent NF kappa B-responsive gene expression, indicating that TAD-truncated p73 alpha activates NF kappa B as does TNF alpha. in addition to the results obtained in the reporter gene assay, TAD-truncated p73a stimulated the translocation of NF kappa B to the nucleus and the expression of an endogenous NF kappa B-responsive gene, Bcl-XL. Taken together, these results demonstrate that TAD-truncated p73 alpha can activate NF kappa B. (c) 2005 Elsevier Inc. All rights reserved.
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