The contribution of transactivation subdomains 1 and 2 to p53-induced gene expression is heterogeneous but not subdomain-specific

Jennifer M Smith, Lawton J Stubbert, Jeffrey D. Hamill and Bruce C McKay

Year 2007, Volume 9, Issue 12

Abstract

Two adjacent regions within the transactivation domain of p53 are sufficient to support sequence-specific transactivation when fused to a heterologous DNA binding domain. It has been hypothesized that these two subdomains of p53 may contribute to the expression of distinct p53-responsive genes. Here we have used oligonucleotide microarrays to identify transcripts induced by variants of p53 with point mutations within subdomains 1, 2 or 1 and 2 (QS1, QS2 and QS1/QS2, respectively). The expression of 254 transcripts was increased in response to wildtype p53 expression but most of these transcripts were poorly induced by these variants of p53. Strikingly, a number of known p53 regulated transcripts including TNFRSF10B, BAX, BTG2 and POLH were increased to wildtype levels by p53QS1 and p53QS2 but not p53QS1/QS2, indicating that either subdomain 1 or 2 is sufficient for p53-dependent expression of a small subset of p53-responsive genes. Unexpectedly, there was no evidence for p53QS1- or p53QS2-specific gene expression. Taken together, we found heterogeneity in the requirement for transactivation subdomains 1 and 2 of p53 without any subdomain-specific contribution to p53-induced gene expression.

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