Anti-apoptosis Proteins Mcl-1 and BcI-xL Have Different p53-Binding   Profiles

doi:10.1021/bi400690m

CORC > 北京大学 > 化学与分子工程学院

	Anti-apoptosis Proteins Mcl-1 and BcI-xL Have Different p53-Binding Profiles
	Yao, Hongwei ; Mi, Shuofu ; Gong, Weibin ; Lin, Jian ; Xu, Nuo ; Perrett, Sarah ; Xia, Bin ; Wang, Jinfeng ; Feng, Yingang
刊名	biochemistry us
	2013
关键词	DNA-BINDING DOMAIN BCL-2 FAMILY PROTEINS TUMOR-SUPPRESSOR P53 CELL-DEATH BH3-ONLY LIGANDS NMR PERMEABILIZATION DISRUPTION COMPLEXES ABT-737
DOI	10.1021/bi400690m
英文摘要	One of the transcription-independent mechanisms of the tumor suppressor p53 discovered in recent years involves physical interaction between p53 and proteins of the Bcl-2 family. In this paper, significant differences between the interaction of p53 with Mcl-1 and Bcl-xL were demonstrated by NMR spectroscopy and isothermal titration calorimetry. Bcl-xL was found to bind strongly to the p53 DNA-binding domain (DBD) with a dissociation constant (K-d) of similar to 600 nM, whereas Mcl-1 binds to the p53 DBD weakly with a dissociation constant in the mM range. In contrast, the p53 transactivation domain (TAD) binds weakly to Bcl-xL with a K-d similar to 300-500 mu M and strongly to Mcl-1 with a K-d similar to 10-20 mu M. NMR titrations indicate that although the p53 TAD binds to the BH3-binding grooves of both Bcl-xL and Mcl-1, Bcl-xL prefers to bind to the first subdomain (TAD1) in the p53 TAD, and Mcl-1 prefers to bind to the second subdomain (TAD2). Therefore, Mcl-1 and Bcl-xL have different p53-binding profiles. This indicates that the detailed interaction mechanisms are different, although both Mcl-1 and Bcl-xL can mediate transcription-independent cytosolic roles of p53. The revealed differences in binding sites and binding affinities should be considered when BH3 mimetics are used in cancer therapy development.; Biochemistry & Molecular Biology; SCI(E); EI; 6; ARTICLE; 37; 6324-6334; 52
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/391038]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Yao, Hongwei,Mi, Shuofu,Gong, Weibin,et al. Anti-apoptosis Proteins Mcl-1 and BcI-xL Have Different p53-Binding Profiles[J]. biochemistry us,2013.
APA	Yao, Hongwei.,Mi, Shuofu.,Gong, Weibin.,Lin, Jian.,Xu, Nuo.,...&Feng, Yingang.(2013).Anti-apoptosis Proteins Mcl-1 and BcI-xL Have Different p53-Binding Profiles.biochemistry us.
MLA	Yao, Hongwei,et al."Anti-apoptosis Proteins Mcl-1 and BcI-xL Have Different p53-Binding Profiles".biochemistry us (2013).