No evidence of direct binding between ursodeoxycholic acid and the p53 DNA-binding domain

作者：Amaral Joana D; Correia Ana R; Steer Clifford J; Gomes Claudio M; Rodrigues Cecilia M P^*

来源：Bioscience Reports, 2010, 30(5): 359-364.

DOI：10.1042/BSR20090107

• apoptosis
• binding
• CD
• murine double minute 2 (Mdm2)
• p53
• ursodeoxycholic acid (UDCA)

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 beta 1-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.

• 出版日期2010-10
• 单位河北医科大学