Caspase-mediated cleavage of C53/LZAP protein causes abnormal microtubule bundling and rupture of the nuclear envelope

	Caspase-mediated cleavage of C53/LZAP protein causes abnormal microtubule bundling and rupture of the nuclear envelope
	Wu, JC; Jiang, H; Luo, SQ; Zhang, MS; Zhang, YH; Sun, F; Huang, S; Li, HL
刊名	CELL RESEARCH
	2013
卷号	23 期号:5 页码:691-704
关键词	C53/LZAP caspase nuclear envelope microtubule apoptosis
通讯作者	Li, HL (reprint author), Georgia Hlth Sci Univ, Ctr Canc, Dept Biochem & Mol Biol, Augusta, GA 30912 USA.,hli@gru.edu
英文摘要	Apoptotic nucleus undergoes distinct morphological and biochemical changes including nuclear shrinkage, chromatin condensation and DNA fragmentation, which are attributed to caspase-mediated cleavage of several nuclear substrates such as lamins. As most of active caspases reside in the cytoplasm, disruption of the nuclear-cytoplasmic barrier is essential for caspases to reach their nuclear targets. The prevailing proposed mechanism is that the increase in the permeability of nuclear pores induced by caspases allows the caspases and other apoptotic factors to diffuse into the nucleus, thereby resulting in the nuclear destruction. Here, we report a novel observation that physical rupture of the nuclear envelope (NE) occurs in the early stage of apoptosis. We found that the NE rupture was caused by caspase-mediated cleavage of C53/LZAP, a protein that has been implicated in various signaling pathways, including NF-kappa B signaling and DNA damage response, as well as tumorigenesis and metastasis. We also demonstrated that C53/LZAP bound indirectly to the microtubule (MT), and expression of the C53/LZAP cleavage product caused abnormal MT bundling and NE rupture. Taken together, our findings suggest a novel role of C53/LZAP in the regulation of MT dynamics and NE structure during apoptotic cell death. Our study may provide an additional mechanism for disruption of the nuclear-cytoplasmic barrier during apoptosis.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	TUMOR-SUPPRESSOR ; BINDING PROTEIN ; APOPTOSIS ; LZAP ; ACTIVATOR ; CDK5 ; C53 ; CHECKPOINT ; INTERACTS ; BREAKDOWN
收录类别	SCI
语种	英语
WOS记录号	WOS:000318483200013
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/387]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wu, JC,Jiang, H,Luo, SQ,et al. Caspase-mediated cleavage of C53/LZAP protein causes abnormal microtubule bundling and rupture of the nuclear envelope[J]. CELL RESEARCH,2013,23(5):691-704.
APA	Wu, JC.,Jiang, H.,Luo, SQ.,Zhang, MS.,Zhang, YH.,...&Li, HL.(2013).Caspase-mediated cleavage of C53/LZAP protein causes abnormal microtubule bundling and rupture of the nuclear envelope.CELL RESEARCH,23(5),691-704.
MLA	Wu, JC,et al."Caspase-mediated cleavage of C53/LZAP protein causes abnormal microtubule bundling and rupture of the nuclear envelope".CELL RESEARCH 23.5(2013):691-704.