UDCA (ursodeoxycholic acid) is used increasingly for the treatment of cholestatic liver diseases. Among other cytoprotective effects, this endogenous bile acid is a potent inhibitor of apoptosis, interfering with both intrinsic and extrinsic apoptotic pathways. In previous studies, we have demonstrated that the transforming growth factor β1-induced E2F-1/Mdm2 (murine double minute 2)/p53 apoptotic pathway was an upstream molecular target of UDCA. In agreement with this, we have recently established p53 as a key molecular target in UDCA prevention of cell death. The tumour suppressor p53 is a well-described transcription factor that induces the expression of multiple different pro-apoptotic gene products. Its regulation involves a variety of signalling proteins and small molecules, and occurs at multiple levels, including transcription, translation and post-translation levels. In the present study, by using different biophysical techniques, we have investigated the possibility of a direct interaction between the p53 core domain, also referred to as the DNA-binding domain, and UDCA. Our in vitro analysis did not provide any evidence for direct binding between the bile acid UDCA and the p53 core domain.
No evidence of direct binding between ursodeoxycholic acid and the p53 DNA-binding domain
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Joana D. Amaral, Ana R. Correia, Clifford J. Steer, Cláudio M. Gomes, Cecília M.P. Rodrigues; No evidence of direct binding between ursodeoxycholic acid and the p53 DNA-binding domain. Biosci Rep 1 October 2010; 30 (5): 359–364. doi: https://doi.org/10.1042/BSR20090107
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