K29-linked ubiquitin signaling regulates proteotoxic stress response and cell cycle
Autor: | Yuanyuan Yu, Seongjin Park, Jingxian Li, Qingyun Zheng, Lei Liu, Yuan Xie, Minglei Zhao, Anthony A. Kossiakoff, Jingyi Fei, Man Pan, Satchal K. Erramilli |
---|---|
Rok vydání: | 2021 |
Předmět: |
Models
Molecular biology Chemistry Ubiquitin-Protein Ligases Cell Cycle Cell Ubiquitination Cell Biology Cell cycle Yeast Protein ubiquitination Cell biology Fight-or-flight response Midbody medicine.anatomical_structure Ubiquitin Downregulation and upregulation Stress Physiological Cell Line Tumor biology.protein medicine Humans Molecular Biology Function (biology) Signal Transduction |
Zdroj: | Nature Chemical Biology. 17:896-905 |
ISSN: | 1552-4469 1552-4450 |
Popis: | Protein ubiquitination shows remarkable topological and functional diversity through the polymerization of ubiquitin via different linkages. Deciphering the cellular ubiquitin code is of central importance to understand the physiology of the cell. Among the eight possible linkages, K29-linked polyubiquitin is a relatively abundant type of polyubiquitin in both human and yeast cells. However, our understanding of its function is rather limited due to the lack of specific binders as tools to detect K29-linked polyubiquitin. In this study, we screened and characterized a synthetic antigen-binding fragment, termed sAB-K29, that can specifically recognize K29-linked polyubiquitin using chemically synthesized K29-linked diubiquitin. We further determined the crystal structure of this fragment bound to the K29-linked diubiquitin, which revealed the molecular basis of specificity. Using sAB-K29 as a tool, we uncovered that K29-linked ubiquitination is involved in different kinds of cellular proteotoxic stress response as well as cell cycle regulation. In particular, we showed that K29-linked ubiquitination is enriched in the midbody and downregulation of the K29-linked ubiquitination signal arrests cells in G1/S phase. |
Databáze: | OpenAIRE |
Externí odkaz: |