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

doi:10.1021/bi400690m

QIBEBT-IR > 代谢物组学研究组

	Anti-apoptosis Proteins Mcl-1 and BcI-xL Have Different p53-Binding Profiles
	Yao, Hongwei 1,4; Mi, Shuofu ; Gong, Weibin 1; Lin, Jian 2; Xu, Nuo 2; Perrett, Sarah 1; Xia, Bin 2; Wang, Jinfeng 1; Feng, Yingang1,3
	2013-09-17
发表期刊	BIOCHEMISTRY
卷号	52 期号:37 页码:6324-6334
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.
文章类型	Article
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
DOI	10.1021/bi400690m
关键词[WOS]	DNA-BINDING DOMAIN ; BCL-2 FAMILY PROTEINS ; TUMOR-SUPPRESSOR P53 ; CELL-DEATH ; BH3-ONLY LIGANDS ; NMR ; PERMEABILIZATION ; DISRUPTION ; COMPLEXES ; ABT-737
收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000330099600004
引用统计	被引频次：24[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qibebt.ac.cn/handle/337004/5983
专题	代谢物组学研究组
作者单位	1.Chinese Acad Sci, Inst Biophys, Nat Lab Biomacromol, Beijing 100101, Peoples R China 2.Peking Univ, Beijing Nucl Magnet Resonance Ctr, Coll Chem & Mol Engn, Beijing 100871, Peoples R China 3.Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Shandong Prov Key Lab Energy Genet, Qingdao 266101, Peoples R China 4.Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China
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,2013,52(37):6324-6334.
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,52(37),6324-6334.
MLA	Yao, Hongwei,et al."Anti-apoptosis Proteins Mcl-1 and BcI-xL Have Different p53-Binding Profiles".BIOCHEMISTRY 52.37(2013):6324-6334.