Ku80 negatively regulates the expression of OCT4 via competitive binding to SALL4 and promoting lysosomal degradation of OCT4 - Details

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Abstract：

SALL4　and　OCT4,　along　with　other　pluripotency-associated　transcription　factors,　play　critical　roles　in　maintaining　embryonic　stem　cell　pluripotency　and　self-renewal.　Ku80　is　a　component　of　the　protein　complex　called　DNA-dependent　protein　kinase,　which　mainly　involved　in　DNA　double-strand　break　repair.　In　this　study,　we　show　evidence　that　Ku80　physically　interacted　with　SALL4.　The　interaction　competitively　disrupts　the　SALL4-OCT4　complex　and　result　in　OCT4　lysosomal　degradation.　Finally,　Ku80　inhibits　self-renewal　and　metastasis　of　hepatocellular　carcinoma　cells　through　breaking　the　SALL4-OCT4　interactions　and　down-regulating　the　expression　of　OCT4.　Our　study　reveal　novel　function　of　Ku80　in　stemness　maintaining　of　cancer　stem　cells　via　its　interaction　with　SALL4　and　highlight　the　double-sidedness　of　Ku80　as　an　anti-cancer　target.　©　2019　Elsevier　Ltd

Keyword：

Ku80; Lysosomal degradation; OCT4; SALL4; Stemness

Community：

[ 1 ] [Zhao, B.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 2 ] [Zhao, B.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 3 ] [Zhao, B.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 4 ] [Zheng, X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 5 ] [Zheng, X.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 6 ] [Tan, X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 7 ] [Tan, X.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 8 ] [Ke, K.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 9 ] [Ke, K.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 10 ] [Wang, F.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 11 ] [Wang, F.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 12 ] [Wang, Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 13 ] [Wang, Y.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 14 ] [Wang, Y.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 15 ] [Xing, X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 16 ] [Xing, X.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 17 ] [Xing, X.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 18 ] [Zhang, C.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 19 ] [Zhang, C.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 20 ] [Zhang, C.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 21 ] [Hu, P.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 22 ] [Hu, P.]School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China
[ 23 ] [Hu, P.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 24 ] [Lan, S.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 25 ] [Lan, S.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 26 ] [Li, Q.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 27 ] [Li, Q.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 28 ] [Huang, A.]School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, China
[ 29 ] [Huang, A.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 30 ] [Liu, X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 31 ] [Liu, X.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 32 ] [Liu, X.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China

Reprint 's Address：

[Liu, X.]Xihong Road 312China

Email：

xiaoloong.liu@gmail.com

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Source ：

International Journal of Biochemistry and Cell Biology

ISSN： 1357-2725

Year： 2020

Volume： 118

5 . 0 8 5

JCR@2020

3 . 4 0 0

JCR@2023

ESI HC Threshold：156

JCR Journal Grade：2

CAS Journal Grade：3

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WoS CC Cited Count：

SCOPUS Cited Count：

ESI Highly Cited Papers on the List： 0 Unfold All

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Chinese Cited Count：

30 Days PV： 0

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