HBO1 catalyzes lysine benzoylation in mammalian cells

Doudou Tan; Wei Wei; Zhen Han; Xuelian Ren; Cong Yan; Shankang Qi; Xiaohan Song; Y George Zheng; Jiemin Wong; He Huang

doi:10.1016/j.isci.2022.105443

HBO1 catalyzes lysine benzoylation in mammalian cells

iScience. 2022 Oct 26;25(11):105443. doi: 10.1016/j.isci.2022.105443. eCollection 2022 Nov 18.

Authors

Doudou Tan¹, Wei Wei², Zhen Han³, Xuelian Ren¹, Cong Yan¹, Shankang Qi¹, Xiaohan Song¹, Y George Zheng³, Jiemin Wong², He Huang^{1

4}

Affiliations

¹ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
² Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
³ Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA.
⁴ University of Chinese Academy of Sciences, Beijing 100049, China.

Abstract

Lysine benzoylation (Kbz) is a newly discovered protein post-translational modification (PTM). This PTM can be stimulated by benzoate and contributes to gene expression. However, its regulatory enzymes and substrate proteins remain largely unknown, hindering further functional studies. Here we identified and validated the lysine acetyltransferase (KAT) HBO1 as a "writer" of Kbz in mammalian cells. In addition, we report the benzoylome in mammalian cells, identifying 1747 Kbz sites; among them at least 77 are the HBO1-targeted Kbz substrates. Bioinformatics analysis showed that HBO1-targeted Kbz sites were involved in multiple processes, including chromatin remodeling, transcription regulation, immune regulation, and tumor growth. Our results thus identify the regulatory elements of the Kbz pathway and reveal the non-canonical enzymatic activity and functions of HBO1 in cellular physiology.

Keywords: Biological sciences; Cell biology; Molecular biology.