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

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	Anti-apoptosis Proteins Mcl-1 and Bcl-xL Have Different p53-Binding Profiles
	Yao, H. ; Mi, S. ; Gong, W. ; Lin, J. ; Xu, N. ; Perrett, S. ; . . . Feng, Y.
刊名	Biochemistry
	2013
卷号	52 期号:37 页码:6324-6334
中文摘要	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 (Kd) of ∼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 Kd ∼ 300−500 μM and strongly to Mcl-1 with a Kd ∼ 10−20 μM. 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 BclxLcan 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.
学科主题	代谢物组学
收录类别	SCI
语种	英语
公开日期	2014-03-24
内容类型	期刊论文
源URL	[http://ir.qibebt.ac.cn:8080/handle/337004/1687]
专题	青岛生物能源与过程研究所_代谢物组学团队
推荐引用方式 GB/T 7714	Yao, H.,Mi, S.,Gong, W.,et al. Anti-apoptosis Proteins Mcl-1 and Bcl-xL Have Different p53-Binding Profiles[J]. Biochemistry,2013,52(37):6324-6334.
APA	Yao, H..,Mi, S..,Gong, W..,Lin, J..,Xu, N..,...&. . . Feng, Y..(2013).Anti-apoptosis Proteins Mcl-1 and Bcl-xL Have Different p53-Binding Profiles.Biochemistry,52(37),6324-6334.
MLA	Yao, H.,et al."Anti-apoptosis Proteins Mcl-1 and Bcl-xL Have Different p53-Binding Profiles".Biochemistry 52.37(2013):6324-6334.