RAE1 promotes BMAL1 shuttling and regulates degradation and activity of CLOCK: BMAL1 heterodimer

被引:21
作者
Zheng, Xulei [1 ,2 ]
Zhao, Xu [1 ,2 ]
Zhang, Yingying [1 ,2 ]
Tan, Hao [1 ,2 ]
Qiu, Bojun [1 ,2 ]
Ma, Tengjiao [1 ,2 ]
Zeng, Jiarong [1 ,2 ]
Tao, Dachang [1 ,2 ]
Liu, Yunqiang [1 ,2 ]
Lu, Yilu [1 ,2 ]
Ma, Yongxin [1 ,2 ]
机构
[1] Sichuan Univ, Dept Med Genet, State Key Lab Biotherapy, West China Hosp, Chengdu 610041, Peoples R China
[2] Collaborat Innovat Ctr, Chengdu 610041, Sichuan, Peoples R China
基金
中国国家自然科学基金;
关键词
CIRCADIAN CLOCK; COMPLEX; PROTEIN; LOCALIZATION; MECHANISMS; COMPONENTS; LIGHT; BUB3; LIMB;
D O I
10.1038/s41419-019-1346-2
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Circadian rhythm is an autoregulatory rhythm, which is sustained by various mechanisms. The nucleocytoplasmic shuttling of BMAL1 is essential for CLOCK translocation between cytoplasm and nucleus and maintenance of the correct pace of the circadian clock. Here we showed that RAE1 and NUP98 can promote the degradation of BMAL1 and CLOCK. Knockdown of RAE1 and NUP98 suppressed BMAL1 shuttling, leading to cytoplasm accumulation of CLOCK. Furthermore, Chip assay showed that knockdown of RAE1 and NUP98 can enhance the interaction between CLOCK: BMAL1 and E-box region in the promoters of Per2 and Cry1 while reducing its transcription activation activity. Our present study firstly revealed that RAE1 and NUP98 are critical regulators for BMAL1 shuttling.
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页数:12
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