p53 isoforms can regulate p53 transcriptional activity.

By J. Bourdon, K. Fernandes, F. Murray-Zmijewski, Geng-Hung Liu, A. Diot, Dimitris P. Xirodimas, M. Saville, David P. Lane. Genes & Development, 2005

852 citations recorded by the source corpus.

The recently discovered p53-related genes, p73 and p63, express multiple splice variants and N-terminally truncated forms initiated from an alternative promoter in intron 3. To date, no alternative promoter and multiple splice variants have been described for the p53 gene. In this study, we show that p53 has a gene structure similar to the p73 and p63 genes. The human p53 gene contains an alternative promoter and transcribes multiple splice variants. We show that p53 variants are expressed in normal human tissue in a tissue-dependent manner. We determine that the alternative promoter is conserved through evolution from Drosophila to man, suggesting that the p53 family gene structure plays an essential role in the multiple activities of the p53 family members. Consistent with this hypothesis, p53 variants are differentially expressed in human breast tumors compared with normal breast tissue. We establish that p53beta can bind differentially to promoters and can enhance p53 target gene expression in a promoter-dependent manner, while Delta133p53 is dominant-negative toward full-length p53, inhibiting p53-mediated apoptosis. The differential expression of the p53 isoforms in human tumors may explain the difficulties in linking p53 status to the biological properties and drug sensitivity of human cancer.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/276964671b693f4019848ed65788cca67b29666d

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Citations in the corpus

p53 Activation by Knockdown Technologies (2007, background): “Interestingly, this truncated form is thought to act as a dominant negative molecule towards full-length p53, as it lacks the transactivation domain and part of the DNA binding domain [21].”
Blinded by the Light: The Growing Complexity of p53. (2009, background): “For example, a p53 isoform (p53β), that can form heterotetramers with wildtype p53, stimulates wild-type p53 binding and activation of the Bax (Bcl-2-associated X protein) gene, but it does not promote p53 activation of p21 expression (Bourdon et al., 2005).”
p53 in health and disease (2007, background): “Some of these results also hint at a possible role for the recently identified N- or C-terminally truncated isoforms of p53 (Ref”
Regulating the p53 pathway: in vitro hypotheses, in vivo veritas (2006, background): “Fourth, as transfections typically use p53 cDNAs, they do not integrate the potential importance of p53 isoform”
Role of p53 in Cell Death and Human Cancers (2011, background): “encodes multiple variants arising from alternative splicing and alternative promoter usage [127, 128].”
p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure–Function Continuum Concept (2016, background): “The p53β isoform is expressed in most normal tissue except for the brain, fetal brain, fetal liver, lung, muscle, prostate, and spinal cord [161].”
p53 ubiquitination: Mdm2 and beyond. (2006, background): “Moreover, the identification of multiple p53 isoforms in vivo that lack an Mdm2 binding domain (Bourdon et al., 2005) also suggests that these isoforms might be degraded in an Mdm2independent fashion.”