No evidence of direct binding between ursodeoxycholic acid and the p53 DNA-binding domain.
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 beta1-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.
Amaral
Joana D
JD
Faculty of Pharmacy, Research Institute for Medicines and Pharmaceutical Sciences, University of Lisbon, Lisbon, Portugal.
Correia
Ana R
AR
Steer
Clifford J
CJ
Gomes
Cláudio M
CM
Rodrigues
Cecília M P
CM
D002756:Cholagogues and Choleretics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000378:metabolism*
D002756:Cholagogues and Choleretics; D016159:Tumor Suppressor Protein p53; D014580:Ursodeoxycholic Acid