TY - JOUR
T1 - Jab1 interacts directly with HIF-1α and regulates its stability
AU - Bae, Moon Kyoung
AU - Ahn, Mee Young
AU - Jeong, Joo Won
AU - Bae, Myung Ho
AU - Lee, You Mie
AU - Bae, Soo Kyung
AU - Park, Jong Wan
AU - Kim, Kwang Rok
AU - Kim, Kyu Won
PY - 2002/1/4
Y1 - 2002/1/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037016769&partnerID=8YFLogxK
U2 - 10.1074/jbc.C100442200
DO - 10.1074/jbc.C100442200
M3 - Article
C2 - 11707426
AN - SCOPUS:0037016769
SN - 0021-9258
VL - 277
SP - 9
EP - 12
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 1
ER -