SCFβ-TRCP promotes cell growth by targeting PR-Set7/Set8 for degradation

被引:35
作者
Wang, Zhiwei [1 ,2 ,3 ]
Dai, Xiangpeng [3 ]
Zhong, Jiateng [3 ,4 ]
Inuzuka, Hiroyuki [3 ]
Wan, Lixin [3 ]
Li, Xiaoning [3 ,5 ]
Wang, Lixia [1 ,2 ]
Ye, Xiantao [1 ,2 ]
Sun, Liankun [5 ]
Gao, Daming [3 ,6 ]
Zou, Lee [7 ]
Wei, Wenyi [3 ]
机构
[1] Soochow Univ, Affiliated Hosp 1, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China
[2] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Hematol, Collaborat Innovat Ctr Hematol, Suzhou 215123, Peoples R China
[3] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA
[4] Xinxiang Med Univ, Dept Pathol, Xinxiang 453000, Peoples R China
[5] Jilin Univ, Basic Med Coll, Dept Pathophysiol, Changchun 130021, Peoples R China
[6] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China
[7] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Canc Ctr, Boston, MA 02129 USA
来源
NATURE COMMUNICATIONS | 2015年 / 6卷
关键词
SCF-BETA-TRCP; HISTONE METHYLTRANSFERASE SET8; UBIQUITIN LIGASE COMPLEX; 3' UNTRANSLATED REGION; MIR-502; BINDING-SITE; DNA-DAMAGE RESPONSE; F-BOX PROTEINS; S-PHASE; DEPENDENT DEGRADATION; GENOME INTEGRITY;
D O I
10.1038/ncomms10185
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
The Set8/PR-Set7/KMT5a methyltransferase plays critical roles in governing transcriptional regulation, cell cycle progression and tumorigenesis. Although CRL4(Cdt2) was reported to regulate Set8 stability, deleting the PIP motif only led to partial resistance to ultravioletinduced degradation of Set8, indicating the existence of additional E3 ligase(s) controlling Set8 stability. Furthermore, it remains largely undefined how DNA damage-induced kinase cascades trigger the timely destruction of Set8 to govern tumorigenesis. Here, we report that SCF beta-TRCP earmarks Set8 for ubiquitination and degradation in a casein kinase I-dependent manner, which is activated by DNA-damaging agents. Biologically, both CRL4(Cdt2) and SCF beta-TRCP-mediated pathways contribute to ultraviolet-induced Set8 degradation to control cell cycle progression, governing the onset of DNA damage-induced checkpoints. Therefore, like many critical cell cycle regulators including p21 and Cdt1, we uncover a tight regulatory network to accurately control Set8 abundance. Our studies further suggest that aberrancies in this delicate degradation pathway might contribute to aberrant elevation of Set8 in human tumours.
引用
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页数:11
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