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Title 

Binding and regulation of hypoxia-inducible factor-1 by the inhibitory PAS proteins

 

저해성 PAS 단백질에 의한 HIF-1a 단백질의 조절

Authors 

Mi Sun JangJae Eun ParkJung A LeeSung Goo ParkP K MyungDo Hee LeeByoung Chul ParkSayeon Cho

Publisher 

Elsevier

Issue Date 

2005

Citation 

Biochemical and Biophysical Research Communications, vol. 337, no. 1, pp. 209-215

Keywords 

angiogenesishypoxiahypoxia-inducible factor-1αinhibitory PAS domain proteinhypoxia inducible factor 1hypoxia inducible factor 1alphaprotein bindingprotein domainprotein functioncell hypoxia

Abstract 

Hypoxia-inducible factor-1 (HIF-1), which consists of oxygen-sensitive HIF-1α and constitutively expressed HIF-1β subunits, activates transcription of genes encoding proteins that mediate adaptive responses to reduced oxygen availability. The mouse inhibitory PAS (Per/Arnt/Sim) domain protein (IPAS) functions as a negative regulator in HIF-mediated gene expression. In this report, we cloned the human orthologs of the mouse IPAS gene, IPASH1 and IPASH2, to further study the regulatory mechanism of HIF-1 by the IPAS proteins. The human IPAS proteins inhibited the transactivation function of HIF-1α under hypoxic conditions. In addition, human IPAS proteins blocked the hypoxia-induced VEGF expression and inhibited cell migration and tube formation of human umbilical vein endothelial cells. Interestingly, both HIF-1α and HIF-1β interacted with the IPAS proteins. Collectively, these results suggest that human IPAS proteins inhibit angiogenesis by binding to and inhibiting HIF-1α and HIF-1β.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2005.09.038

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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