B55
Characterisation of mouse p53 isoforms
Marie Khoury1, Kenneth Fernandes1, David Lane1, Anne-Catherine Prats2, Jean-Christophe Bourdon1
1University of Dundee, UK, 2Inserm U589, Toulouse, France
Our laboratory has previously identified p53 isoforms in human and drosophila cells and highlighted an association of some p53 isoforms with survival in cancer patients. We also showed that p53 isoforms modulate p53 transcriptional and tumour suppressor activities.
In this study, we report that the mouse p53 gene expresses 6 different p53 isoforms (p53, p53AS, ∆40p53, ∆40p53AS, ∆157p53 and ∆157p53AS). We confirm the alternative splicing of the intron-10 leading to p53AS expression as previously described (Wolf et al, 1985). We determine that ∆40p53 isoforms are due to a cryptic splicing site in the intron-2 while the ∆157p53 isoforms are due to initiation of transcription from the intron-4 of the mouse p53 gene.
To investigate the biological activities of mouse p53 isoforms, we raised novel antibodies, designed specific siRNAs and constructed expression vectors for each mouse p53 isoform. We will present data showing their effects on cell cycle and apoptosis in the absence or presence of DNA damaging agents.
