Binding and regulation of hypoxia-inducible factor-1 by the inhibitory PAS proteins = 저해성 PAS 단백질에 의한 HIF-1a 단백질의 조절

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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
Author(s)
Mi Sun Jang; Jae Eun Park; Jung A Lee; Sung Goo Park; P K Myung; Do Hee Lee; Byoung Chul Park; Sayeon Cho
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 337, no. 1, pp. 209-215
Publication Year
2005
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.
Keyword
AngiogenesisHypoxiaHypoxia-inducible factor-1αInhibitory PAS domain protein
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbrc.2005.09.038
Type
Article
Appears in Collections:
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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