The nucleolus functions as the compartment for histone H2B protein degradation

Yanping Liu; Yufei Wang; Lu Yang; Feng Sun; Sheng Li; Yequan Wang; Guo-An Zhang; Tingting Dong; Lei-Lei Zhang; Wanglin Duan; Xiaojun Zhang; Wen Cui; Su Chen

doi:10.1016/j.isci.2021.102256

The nucleolus functions as the compartment for histone H2B protein degradation

iScience. 2021 Mar 2;24(4):102256. doi: 10.1016/j.isci.2021.102256. eCollection 2021 Apr 23.

Authors

Yanping Liu¹, Yufei Wang¹, Lu Yang¹, Feng Sun², Sheng Li³, Yequan Wang³, Guo-An Zhang³, Tingting Dong³, Lei-Lei Zhang³, Wanglin Duan¹, Xiaojun Zhang⁴, Wen Cui³, Su Chen^{1

3

4

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Affiliations

¹ Laboratory of Molecular and Cellular Biology, School of Forensic Sciences, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi 710061, PR China.
² Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, Shanghai 200092, PR China.
³ School of Forensic Sciences and Laboratory Medicine, Jining Medical University, Jining, Shandong 272067, PR China.
⁴ Department of Science and Education, People's Hospital of Zunhua, Tangshan, Hebei 064200, PR China.
⁵ Laboratory of Molecular and Cellular Biology, School of Basic Medical Sciences, Henan University School of Medicine, Kaifeng, Henan 475004, PR China.

Abstract

Histones are main components of chromatin, and the protein levels of histones significantly affect chromatin assembly. However, how histone protein levels are regulated, especially whether and how histones are degraded, is largely unclear. Here, we found that histone H2B is mainly degraded through the proteasome-mediated pathway, and the lysine-120 site of H2B is essential for its K48-linked polyubiquitination and degradation. Moreover, the degradation-impaired H2BK120R mutant shows an increased nucleolus localization, and inhibition of the proteasome results in an elevated nucleolus distribution of wild-type H2B, which is similar to that of H2BK120R mutants. More importantly, the nucleolus fractions can ubiquitinate and degrade the purified H2B in vitro, suggesting that the nucleolus, in addition to its canonical roles regulating ribosome genesis and protein translation, likely associates with H2B degradation. Therefore, these findings revealed a novel mechanism for the regulation of H2B degradation in which a nucleolus-associated proteasome pathway is involved.

Keywords: Biochemistry; Cell Biology.