Wang Mengdong, Wang Di, Lang Yue, Shao Anwen, Zhang Rui, Tang Jun, Lai Dongming, Xiao Chenglu
National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Sun Yat-sen Memorial Hospital, Sun Yat-sen University, NO. 107, Yanjiangxi Road, Guangzhou, 510120, China.
Heliyon. 2023 Jan 24;9(2):e13222. doi: 10.1016/j.heliyon.2023.e13222. eCollection 2023 Feb.
HIF-1α plays a crucial part in hypoxia response by transcriptionally upregulating genes to adapt the hypoxic condition. HIF-1α is under severe cellular control as its exceptional activation is always associated with tumorigenesis and tumor progression. Here, we report L3MBTL3 serves as a novel negative regulator of HIF-1α. It is upregulated during hypoxia and acts as a transcriptional target of HIF-1α. In the nuclei, L3MBTL3 makes an interaction with HIF-1α and promotes its ubiquitination and degradation. These findings indicate L3MBTL3 forms a negative feedback loop with HIF-1α in vitro to dampen the hypoxic response.
缺氧诱导因子-1α（HIF-1α）通过转录上调基因以适应缺氧状态，在缺氧反应中发挥关键作用。HIF-1α受到严格的细胞调控，因为其异常激活总是与肿瘤发生和肿瘤进展相关。在此，我们报道L3MBTL3作为HIF-1α的一种新型负调节因子。它在缺氧期间上调，并作为HIF-1α的转录靶点发挥作用。在细胞核中，L3MBTL3与HIF-1α相互作用，促进其泛素化和降解。这些发现表明，L3MBTL3在体外与HIF-1α形成负反馈环以减弱缺氧反应。
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