Jab1 interacts directly with HIF-1α and regulates its stability

Moon Kyoung Bae, Mee Young Ahn, Joo Won Jeong, Myung Ho Bae, You Mie Lee, Soo Kyung Bae, Jong Wan Park, Kwang Rok Kim, Kyu Won Kim

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a master transcription factor that controls transcriptional activation of a number of genes responsive to the low cellular oxygen tension, including vascular endothelial growth factor (VEGF), erythropoietin, and glycolytic enzymes. The stability and activity of HIF-1α are regulated by binding to various proteins such as pVHL, p53, and p300/CBP. Here, using the yeast two-hybrid screening system, we found that HIF-1α interacts with Jab1 (Jun activation domain-binding protein-1), which is a coactivator of AP-1 transcription factor and fifth subunit of COP9 signalosome complex. The interaction of Jab1 with HIF-1α was confirmed by GST pull-down assay and also reproduced in vivo in HEK 293 cells, where endogenous Jab1 was coimmunoprecipitated with the overexpressed HIF-1α. Moreover, Jab1-enhanced transcriptional activity of HIF-1 under hypoxia led to increase the expression of VEGF, a major HIF-1α target gene. Furthermore, Jab1 increased HIF-1α protein levels, which was due to the enhanced HIF-1α stability. The binding of HIF-1α and p53 tumor suppressor protein, negative regulator of HIF-1α stability, was interfered in a Jab1-dependent manner. Taken together, these results indicate that Jab1 should be considered as a novel regulator of HIF-1α stability via direct interaction.

Original languageEnglish
Pages (from-to)9-12
Number of pages4
JournalJournal of Biological Chemistry
Volume277
Issue number1
DOIs
StatePublished - 4 Jan 2002

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