SUMOylation Fine-Tunes Endothelial HEY1 in the Regulation of Angiogenesis

作者：Ruizhe Ren, Sha Ding, Kefan Ma, Yuan‐Qing Jiang, Yiran Wang, Junbo Chen, Yunyun Wang, Yaohui Kou, Fan Xiao, Xiaolong Zhu, Lingfeng Qin, Cong Qiu, Michael Simons, Xiyang Wei, Luyang Yu · 发表于：Circulation Research · 年份：2024 · DOI：10.1161/circresaha.123.323398 · 被引用次数：26 · 研究领域：Ubiquitin and proteasome pathways、Developmental Biology and Gene Regulation、interferon and immune responses

BACKGROUND: Angiogenesis, which plays a critical role in embryonic development and tissue repair, is controlled by a set of angiogenic signaling pathways. As a TF (transcription factor) belonging to the basic helix-loop-helix family, HEY (hairy/enhancer of split related with YRPW motif)-1 (YRPW motif, abbreviation of 4 highly conserved amino acids in the motif) has been identified as a key player in developmental angiogenesis. However, the precise mechanisms underlying HEY1's actions in angiogenesis remain largely unknown. Our previous studies have suggested a potential role for posttranslational SUMOylation in the dynamic regulation of vascular development and organization. METHODS: Immunoprecipitation, mass spectrometry, and bioinformatics analysis were used to determine the biochemical characteristics of HEY1 SUMOylation. The promoter-binding capability of HEY1 was determined by chromatin immunoprecipitation, dual luciferase, and electrophoretic mobility shift assays. The dimerization pattern of HEY1 was determined by coimmunoprecipitation. The angiogenic capabilities of endothelial cells were assessed by CCK-8 (cell counting kit-8), 5-ethynyl-2-deoxyuridine staining, wound healing, transwell, and sprouting assays. Embryonic and postnatal vascular growth in mouse tissues, matrigel plug assay, cutaneous wound healing model, oxygen-induced retinopathy model, and tumor angiogenesis model were used to investigate the angiogenesis in vivo. RESULTS: We identified intrinsic endot...