Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains

Ghioni, Pamela, Bolognese, Fabrizio, Duijf, Pascal H. G., van Bokhoven, Hans, Mantovani, Roberto and Guerrini, Luisa (2002) Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains. Molecular and Cellular Biology, 22 24: 8659-8668. doi:10.1128/MCB.22.24.8659-8668.2002

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Author Ghioni, Pamela
Bolognese, Fabrizio
Duijf, Pascal H. G.
van Bokhoven, Hans
Mantovani, Roberto
Guerrini, Luisa
Title Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains
Journal name Molecular and Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
Publication date 2002-12-01
Sub-type Article (original research)
DOI 10.1128/MCB.22.24.8659-8668.2002
Open Access Status File (Publisher version)
Volume 22
Issue 24
Start page 8659
End page 8668
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
p63 is a transcription factor structurally related to the p53 tumor suppressor. The C-terminal region differs from p53's in that it contains a sterile alpha motif (SAM) domain and is subject to multiple alternative splicings. The N-terminal region is present in the transactivation (TA) and ΔN configurations, with the latter lacking the transcriptional activation domain 1. Single amino acid substitutions and frameshift mutations of p63 cause the human ankyloblepharon ectodermal dysplasia clefting (AEC) or ectrodactyly ectodermal dysplasia and facial clefting (EEC) syndromes. We have systematically compared the activities of the wild-type p63 isoforms and of the natural mutants in activation and repression assays on three promoters modulated by p53. We found that p63 proteins with an altered SAM domain or no SAM domain—the β isoforms, the EEC frameshift mutant, and the missense AEC mutations—all showed a distinctly higher level of activation of the MDM2 promoter and decreased repression on the HSP70 promoter. Fusion of SAM to the GAL4 DNA-binding domain repressed a heterologous promoter. A second activation domain, TA2, corresponding to exons 11 to 12, was uncovered by comparing the activation of ΔN isoforms on natural promoters and in GAL4 fusion systems. In colony formation assays, the AEC mutants, but not the EEC frameshift, were consistently less efficient in suppressing growth, in both the TA version and the ΔN version, with respect to their p63α counterparts. These data highlight the modularity of p63, identifying the SAM domain as a dominant transcriptional repression module and indicating that the AEC and EEC frameshift mutants are characterized by a subversion of the p63 transcriptional potential.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 167 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 06 Dec 2013, 01:35:05 EST by Pascal Duijf on behalf of UQ Diamantina Institute