Markowitz Joseph, Mackerell Alexander D, Carrier France, Charpentier Thomas H, Weber David J
University of Maryland School of Medicine, Department of Biochemistry and Molecular Biology, Maryland 21201, USA.
Curr Top Med Chem. 2005;5(12):1093-108. doi: 10.2174/156802605774370865.
S100B interacts with the p53 protein in a calcium-dependent manner and down-regulates its function as a tumor suppressor. Therefore, inhibiting the S100B-p53 interaction represents a new approach for restoring functional wild-type p53 in cancers with elevated S100B such as found in malignant melanoma. A discussion of the biological rational for targeting S100B and a description of methodologies relevant to the discovery of compounds that inhibit S100B-p53 binding, including computational techniques, structural biology techniques, and cellular assays, is presented.
S100B以钙依赖的方式与p53蛋白相互作用，并下调其作为肿瘤抑制因子的功能。因此，抑制S100B与p53的相互作用代表了一种在S100B升高的癌症（如恶性黑色素瘤）中恢复功能性野生型p53的新方法。本文讨论了靶向S100B的生物学原理，并描述了与发现抑制S100B-p53结合的化合物相关的方法，包括计算技术、结构生物学技术和细胞分析。
