Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquitination and degradation of CENP-A during the cell cycle.
Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquitination and degradation of CENP-A during the cell cycle.
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DOI：
10.1016/j.celrep.2021.109987
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发表时间：
2021-11
期刊：
影响因子：
8.8
通讯作者：
Kehui Wang;Yuting Liu;Zhouliang Yu;Bo Gu;Jie Hu;Li Huang;Xiao Ge;Lingyi Xu;Mengyu Zhang;Jicheng Zhao;Mingli Hu;Rongrong Le;Qiang Wu;Shenglong Ye;Shaorong Gao;Xiao-Dong Zhang;Rui-Ming Xu;Guohong Li
中科院分区：
文献类型：
--
作者：
Kehui Wang;Yuting Liu;Zhouliang Yu;Bo Gu;Jie Hu;Li Huang;Xiao Ge;Lingyi Xu;Mengyu Zhang;Jicheng Zhao;Mingli Hu;Rongrong Le;Qiang Wu;Shenglong Ye;Shaorong Gao;Xiao-Dong Zhang;Rui-Ming Xu;Guohong Li
CENP-A (centromeric protein A), a histone H3 variant, specifies centromere identity and is essential to centromere maintenance. Little is known about how protein levels of CENP-A are controlled in mammalian cells. Here, we report that the phosphorylation of CENP-A Ser68 primes the ubiquitin-proteasome-mediated proteolysis of CENP-A during mitotic phase in human cultured cells. We identify two major polyubiquitination sites that are responsible for this phosphorylation-dependent degradation. Substituting the two residues, Lys49 and Lys124, with arginines abrogates proper CENP-A degradation and results in CENP-A mislocalization to non-centromeric regions. Furthermore, we find that DCAF11 (DDB1 and CUL4 associated factor 11/WDR23) is the E3 ligase that specifically mediates the observed polyubiquitination. Deletion of DCAF11 hampers CENP-A degradation and causes its mislocalization. We conclude that the Ser68 phosphorylation plays an important role in regulating cellular CENP-A homeostasis via DCAF11-mediated degradation to prevent ectopic localization of CENP-A during the cell cycle.
