Lamin A buffers CK2 kinase activity to modulate aging in a progeria mouse model

被引：26

作者：

Ao, Ying ^{[1
,4
]}

Zhang, Jie ^{[1
]}

Liu, Zuojun ^{[1
]}

Qian, Minxian ^{[1
]}

Li, Yao ^{[2
]}

Wu, Zhuping ^{[1
]}

Sun, Pengfei ^{[1
]}

Wu, Jie ^{[1
]}

Bei, Weixin ^{[1
]}

Wen, Junqu ^{[1
]}

Wu, Xuli ^{[2
]}

Li, Feng ^{[4
]}

Zhou, Zhongjun ^{[3
]}

Zhu, Wei-Guo ^{[1
]}

Liu, Baohua ^{[1
]}

Wang, Zimei ^{[1
]}

机构：

[1] Hlth Sci Ctr, Guangdong Key Lab Genome Stabil & Human Dis Preve, Carson Int Canc Ctr, Dept Biochem & Mol Biol,Sch Basic Med Sci, Shenzhen 518060, Peoples R China

[2] Shenzhen Univ, Sch Publ Hlth, Hlth Sci Ctr, Shenzhen 518060, Peoples R China

[3] Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, 21 Sassoon Rd, Hong Kong, Peoples R China

[4] Wuhan Univ, Sch Basic Med Sci, Dept Genet, Wuhan 430071, Hubei, Peoples R China

来源：

SCIENCE ADVANCES | 2019年 / 5卷 / 03期

基金：

中国国家自然科学基金;

关键词：

PROTEIN-KINASE; NUCLEAR-MATRIX; AMELIORATES DISEASE; BETA-SUBUNIT; INHIBITOR; PHOSPHORYLATES; SENESCENCE; EXPRESSION; MECHANISM; AUTOPHAGY;

D O I：

10.1126/sciadv.aav5078

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Defective nuclear lamina protein lamin A is associated with premature aging. Casein kinase 2 (CK2) binds the nuclear lamina, and inhibiting CK2 activity induces cellular senescence in cancer cells. Thus, it is feasible that lamin A and CK2 may cooperate in the aging process. Nuclear CK2 localization relies on lamin A and the lamin A carboxyl terminus physically interacts with the CK2 alpha catalytic core and inhibits its kinase activity. Loss of lamin A in Lmna-knockout mouse embryonic fibroblasts (MEFs) confers increased CK2 activity. Conversely, prelamin A that accumulates in Zmpste24-deficent MEFs exhibits a high CK2 alpha binding affinity and concomitantly reduces CK2 kinase activity. Permidine treatment activates CK2 by releasing the interaction between lamin A and CK2, promoting DNA damage repair and ameliorating progeroid features. These data reveal a previously unidentified function for nuclear lamin A and highlight an essential role for CK2 in regulating senescence and aging.

引用

页数：12

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