L3MBTL3 is induced by HIF-1α and fine tunes the HIF-1α degradation under hypoxia in vitro

Mengdong Wang; Di Wang; Yue Lang; Anwen Shao; Rui Zhang; Jun Tang; Dongming Lai; Chenglu Xiao

doi:10.1016/j.heliyon.2023.e13222

L3MBTL3 is induced by HIF-1α and fine tunes the HIF-1α degradation under hypoxia in vitro

Heliyon. 2023 Jan 24;9(2):e13222. doi: 10.1016/j.heliyon.2023.e13222. eCollection 2023 Feb.

Authors

Mengdong Wang¹, Di Wang¹, Yue Lang¹, Anwen Shao¹, Rui Zhang¹, Jun Tang¹, Dongming Lai², Chenglu Xiao¹

Affiliations

¹ National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
² Sun Yat-sen Memorial Hospital, Sun Yat-sen University, NO. 107, Yanjiangxi Road, Guangzhou, 510120, China.

Abstract

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.

Keywords: ARNT, aryl hydrocarbon receptor nuclear translocator; CHX, cycloheximide; FCS, phenylalanine-cysteine-serine nucleic acid−binding; HIF-1, hypoxia inducible factor 1; HIF-1α; HIF-1α degradation; HRE, hypoxia response element; Hypoxia; L3MBTL3; L3MBTL3, lethal (3) malignant brain tumor-like 3; MBT, malignant brain tumor; PHD, prolyl hydroxylase domain; SAM, sterile α motif; VHL, von Hippel-Lindau.