ULK1 inhibitor induces spindle microtubule disorganization and inhibits phosphorylation of Ser10 of histone H3

doi:10.1002/2211-5463.13000

	ULK1 inhibitor induces spindle microtubule disorganization and inhibits phosphorylation of Ser10 of histone H3
	Ji, Xinmiao 2; Zhang, Xin 1,2; Li, Zhiyuan 2
刊名	FEBS OPEN BIO
	2020-11-01
卷号	10
关键词	autophagy mitosis MRT68921 polyploidy SBI‐ 0206965 ULK1 inhibitor
ISSN号	2211-5463
DOI	10.1002/2211-5463.13000
通讯作者	Li, Zhiyuan(lizhiyuan@hmfl.ac.cn)
英文摘要	Certain tumors are dependent on autophagy for survival; thus, the use of unc-51-like autophagy activating kinase (ULK) 1 inhibitors to block autophagy has the potential for tumor treatment. However, ULK1 inhibitors affect processes other than autophagy. Herein, we report that the ULK1 inhibitors SBI-0206965/MRT68921 not only inhibit phosphorylation of histone H3 (Ser10) and delay chromatin condensation but also induce spindle microtubule disorganization to form short and fragmented microtubule polymers. Although the delay in chromatin condensation also delayed mitotic entry, the disorganized microtubule polymers resulted in unsegregated chromosomes and polyploidy. Although the effect on mitotic entry was moderate, polyploidy formation was decreased in ULK1 knockout cells with or without ULK2 knockdown. In conclusion, it will be helpful to consider the roles of ULK1 inhibitors in mitotic dysregulation, as well as autophagy, when evaluating their antitumor efficacy.
资助项目	National Natural Science Foundation of China[31900508] ; Anhui Natural Science Foundation[1908085MC88] ; CASHIPS Director's Fund[YZJJ2019QN17]
WOS关键词	AURORA-B ; AUTOPHAGY ; CELLS ; AMPK ; APOPTOSIS ; KINASES ; COMPLEX ; MITOSIS ; GROWTH ; ENTRY
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	WILEY
WOS记录号	WOS:000584406700017
资助机构	National Natural Science Foundation of China ; Anhui Natural Science Foundation ; CASHIPS Director's Fund
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/104857]
专题	中国科学院合肥物质科学研究院
通讯作者	Li, Zhiyuan
作者单位	1.Anhui Univ, Inst Phys Sci & Informat Technol, Hefei, Peoples R China 2.Chinese Acad Sci, Hefei Inst Phys Sci, High Magnet Field Lab, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei 230031, Anhui, Peoples R China
推荐引用方式 GB/T 7714	Ji, Xinmiao,Zhang, Xin,Li, Zhiyuan. ULK1 inhibitor induces spindle microtubule disorganization and inhibits phosphorylation of Ser10 of histone H3[J]. FEBS OPEN BIO,2020,10.
APA	Ji, Xinmiao,Zhang, Xin,&Li, Zhiyuan.(2020).ULK1 inhibitor induces spindle microtubule disorganization and inhibits phosphorylation of Ser10 of histone H3.FEBS OPEN BIO,10.
MLA	Ji, Xinmiao,et al."ULK1 inhibitor induces spindle microtubule disorganization and inhibits phosphorylation of Ser10 of histone H3".FEBS OPEN BIO 10(2020).