Quantitative Proteomics Reveals the Role of Lysine 2-Hydroxyisobutyrylation Pathway Mediated by Tip60

Author:

Wang Ning1,Jiang Yue23,Peng Ping4,Liu Guobin35,Qi Shankang3ORCID,Liu Kun2ORCID,Mei Qi4ORCID,Li Jian6

Affiliation:

1. Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

2. School of Mechanical Engineering and Automation, Northeastern University, Shenyang 110819, China

3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

4. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

5. School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China

6. Institute of Molecular Medicine and Experimental Immunology, University Clinic of Rheinische Friedrich-Wilhelms-University, Germany

Abstract

Lysine 2-hydroxyisobutyrylation (Khib) is a new type of posttranslational modifications (PTMs) extensively reported on eukaryotic cell histones. It is evolutionarily conserved and participates in diverse important biological processes, such as transcription and cell metabolism. Recently, it has been demonstrated that Khib can be regulated by p300 and Tip60. Although the specific Khib substrates mediated by p300 have been revealed, how Tip60 regulates diverse cellular processes through the Khib pathway and the different roles between Tip60 and p300 in regulating Khib remain largely unknown, which prevents us from understanding how this modification executes its biological functions. In this study, we report the first Khib proteome mediated by Tip60. In total, 3502 unique Khib sites from 1050 proteins were identified. Among them, 536 Khib sites from 406 proteins were present only in Tip60 overexpressing cells and 13 Khib sites increased more than 2-fold in response to Tip60 overexpression, indicating that Tip60 significantly affected global Khib. Notably, only 5 of the 549 Tip60-targeted Khib sites overlapped with the 149 known Khib sites targeted by p300, indicating the different Khib substrate preferences of Tip60 and p300. In addition, the Khib substrates regulated by Tip60 are deeply involved in processes such as nucleic acid metabolism and translation, and some are associated with Parkinson’s and Prion diseases. In summary, our research reveals the Khib substrates targeted by Tip60, which elucidates the effect of Tip60 in regulating various cellular processes through the Khib pathway, and proposes novel views into the functional mechanism of Tip60.

Funder

Ministry of Education of the People's Republic of China

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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