Abstract:
:-The vascular endothelial growth factor receptor Flk-1/KDR is highly expressed during development and almost disappears in adult tissues. Despite its biological relevance, little is known about the molecular mechanisms controlling its expression. In the present work, it is shown that cAMP response element binding protein (CREB) and nuclear factor-kappaB (NF-kappaB)-related antigens bind specific sequences in the Flk-1/KDR promoter. Functional studies demonstrate that cAMP represses whereas tumor necrosis factor-alpha, an activator of NF-kappaB, stimulates promoter activity. Histone acetyltransferases (HATs) P/CAF and CBP/p300 together with p65/RelA, the catalytic subunit of NF-kappaB, increase Flk-1/KDR promoter activity 10- to 20-fold. Consistently, inhibition by cAMP is reverted by increasing intracellular HATs and is completely abolished by site-specific mutagenesis of the cAMP response element. In contrast, specific mutations in the NF-kappaB response element abolish responsiveness to p65/RelA and HATs without affecting cAMP-dependent repression. These results suggest that opposing signaling pathways, activating NF-kappaB or CREB and requiring HAT molecules, control Flk-1/KDR promoter activity.
journal_name
Circ Resjournal_title
Circulation researchauthors
Illi B,Puri P,Morgante L,Capogrossi MC,Gaetano Csubject
Has Abstractpub_date
2000-06-23 00:00:00pages
E110-7issue
12eissn
0009-7330issn
1524-4571journal_volume
86pub_type
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journal_title:Circulation research
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doi:10.1161/CIRCRESAHA.107.154351
更新日期:2007-11-26 00:00:00
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doi:10.1161/01.res.0000054625.24468.08
更新日期:2003-02-21 00:00:00
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pub_type: 杂志文章
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更新日期:1998-01-09 00:00:00
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章,评审
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更新日期:2015-01-16 00:00:00
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更新日期:2006-07-07 00:00:00
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更新日期:1995-03-01 00:00:00
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更新日期:1982-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:1986-08-01 00:00:00