Monoclonal antibody‐based systematic identification of SUMO1‐modification sites reveals TFII‐I SUMOylation is involved in tumor growth

Abstract

SUMOylation plays an essential role in diverse physiological and pathological processes. Identification of wild‐type SUMO1‐modification sites by mass spectrometry is still challenging. In this study, we produced a monoclonal SUMO1C‐K antibody recognizing SUMOylated peptides and proposed an efficient streamline for identification of SUMOylation sites. We identified 471 SUMOylation sites in 325 proteins from five raw data. These identified sites exhibit a high positive rate when evaluated by mutation‐verified SUMOylation sites. We identified many SUMOylated proteins involved in mitochondrial metabolism and non‐membrane‐bounded organelles formation. We proposed a SUMOylation motif, ΨKXD/EP, where proline is required for efficient SUMOylation. We further revealed SUMOylation of TFII‐I was stimulated by growth signals and was required for nucleus‐localization of p‐ERK1/2. Mutation of SUMOylation sites of TFII‐I suppressed tumor cell growth in vitro and in vivo. Taken together, we provided a strategy for personalized identification of wild‐type SUMO1‐modification sites and revealed the physiological significance of TFII‐I SUMOylation in this study.

P66Shc Mediates SUMO2-induced Endothelial Dysfunction

“…We detected a missed cleavage at a lysine (K) residue as shown in the figure 3B, which was followed by a QTGG modification with a mass of 343.15 Da. This specific mass shift was consistent with the expected tryptic peptide from sumoylated peptide as shown by other studies 38,39 .…”

Protein modifications and diseases

“…Using this monoclonal antibody-based systematic identification of SUMO1modification sites by LC-MS, the authors proposed an efficient streamline to identify protein SUMOylation sites and revealed TFII-I can be SUMOylated to affect tumor growth (Chen et al, 2023). This study provides a strategy to identify wild-type SUMO1-modification sites (Chen et al, 2023). Moreover, Joo et al (2023) uncovered ubiquitin E3 ligase β-TrCP2 as a new master regulator of carbohydrate and lipid metabolism.…”

“…Their findings suggest SIRT6-PPARα-mediated lipid catabolism as a potential therapeutic target for diseases associated with pulmonary fibrosis (He et al, 2023). This special issue also includes original research articles to identify new targets of protein SUMOylation and ubiquitination (Chen et al, 2023;Joo et al, 2023). Chen et al ( 2023) produced a monoclonal SUMO1C-K antibody recognizing SUMOylated peptides.…”

“…Chen et al ( 2023) produced a monoclonal SUMO1C-K antibody recognizing SUMOylated peptides. Using this monoclonal antibody-based systematic identification of SUMO1modification sites by LC-MS, the authors proposed an efficient streamline to identify protein SUMOylation sites and revealed TFII-I can be SUMOylated to affect tumor growth (Chen et al, 2023). This study provides a strategy to identify wild-type SUMO1-modification sites (Chen et al, 2023).…”