N-terminal Sumoylation of Centromeric Histone H3 Variant Cse4 Regulates Its Proteolysis To Prevent Mislocalization to Non-centromeric Chromatin.
N-terminal Sumoylation of Centromeric Histone H3 Variant Cse4 Regulates Its Proteolysis To Prevent Mislocalization to Non-centromeric Chromatin.
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DOI：
10.1534/g3.117.300419
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发表时间：
2018-03-28
期刊：
影响因子：
--
通讯作者：
Basrai MA
中科院分区：
文献类型：
--
作者：
Ohkuni K;Levy-Myers R;Warren J;Au WC;Takahashi Y;Baker RE;Basrai MA
Stringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4. In this study, we have identified lysine 65 (K65) in Cse4 as a site that regulates sumoylation and ubiquitin-mediated proteolysis of Cse4 by Slx5. Strains expressing cse4 K65R exhibit reduced levels of sumoylated and ubiquitinated Cse4 in vivo. Furthermore, co-immunoprecipitation experiments reveal reduced interaction of cse4 K65R with Slx5, leading to increased stability and mislocalization of cse4 K65R under normal physiological conditions. Based on the increased stability of cse4 K65R in psh1∆ strains but not in slx5∆ strains, we conclude that Slx5 targets sumoylated Cse4 K65 for ubiquitination-mediated proteolysis independent of Psh1. In summary, we have identified and characterized the physiological role of Cse4 K65 in sumoylation, ubiquitin-mediated proteolysis, and localization of Cse4 for genome stability.
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影响因子：
37.3
作者：
Amato A;Schillaci T;Lentini L;Di Leonardo A
通讯作者：
Di Leonardo A
影响因子：
16
作者：
Hewawasam G;Shivaraju M;Mattingly M;Venkatesh S;Martin-Brown S;Florens L;Workman JL;Gerton JL
通讯作者：
Gerton JL
DOI：
10.1007/978-3-319-50044-7_10
发表时间：
2017-01-01
期刊：
SUMO REGULATION OF CELLULAR PROCESSES, 2ND EDITION
影响因子：
--
作者：
Mukhopadhyay, Debaditya;Dasso, Mary
通讯作者：
Dasso, Mary
影响因子：
3.3
作者：
Ohkuni, Kentaro;Abdulle, Rashid;Kitagawa, Katsumi
通讯作者：
Kitagawa, Katsumi
影响因子：
10.5
作者：
Deyter GM;Biggins S
通讯作者：
Biggins S