FGF11은 저산소 상태에서 HIF-1a 안정성 증진 인자로써의 역할을 한다

Abstract

Fibroblast growth factor 11 (FGF11) is a member of intracellular FGFs. Although induction of FGF11 by hypoxia has been observed in several cell types, molecular function of FGF11 is not clearly understood yet. This study aimed to investigate the role of FGF11 under hypoxia. Immunoprecipitation and mass spectrometry analysis showed that many interacting partners for FGF11 are related with ubiquitination regulatory mechanism. And we found hypoxia-inducible factors-1&#61537 (HIF-1a) as a binding partner of FGF11. FGF11 knockdown decreased HIF-1a protein, while FGF11 overexpression increased it, without affecting HIF-1a mRNA. FGF11 knockdown increased ubiquitination levels of HIF-1a and decreased its stability, while FGF11 overexpression decreased ubiquitination levels of HIF-1a and increased its stability. These results suggest a cross-regulation between HIF-1a and FGF11, through which hypoxia-induced FGF11 reinforces hypoxia responses by enhancing the stability of HIF-1a.e the role of FGF11 under hypoxia. Immunoprecipitation and mass spectrometry analysis showed that many interacting partners for FGF11 are related with ubiquitination regulatory mechanism. And we found hypoxia-inducible factors-1&#61537 (HIF-1a) as a binding partner of FGF11. FGF11 knockdown decreased HIF-1a protein, while FGF11 overexpression increased it, without affecting HIF-1a mRNA. FGF11 knockdown increased ubiquitination levels of HIF-1a and decreased its stability, while FGF11 overexpression decreased ubiquitination levels of HIF-1a and increased its stability. These results suggest a cross-regulation between HIF-1a and FGF11, through which hypoxia-induced FGF11 reinforces hypoxia responses by enhancing the stability of HIF-1a.