Regulation of platelet-derived growth factor-A chain by Krüppel-like factor 5: new pathway of cooperative activation with nuclear factor-kappaB.
The transcription factor Krüppel-like factor 5 (KLF5) and its genetically downstream target gene platelet-derived growth factor-A (PDGF-A) chain are key factors in regulation of cardiovascular remodeling in response to stress. We show that KLF5 mediates a novel distinct delayed persistent induction of PDGF-A chain in response to the model agonist, phorbol ester, through a cis-element previously shown to mediate phorbol ester induction on to PDGF-A chain through the early growth response factor (Egr-1). Interestingly, the nuclear factor-kappaB (NF-kappaB) p50 subunit further cooperatively activates PDGF-A chain through protein-protein interaction with KLF5 but not Egr-1. RNA interference analysis confirmed that KLF5 and p50 are important for induction of PDGF-A chain. Collectively, we identify a novel regulatory pathway in which PDGF-A chain gene expression, under the control of KLF5, is cooperatively activated by the NF-kappaB p50 subunit and a pathophysiological stimulus.
Department of Cardiovascular Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Kenichi
K
Aizawa
Toru
T
Suzuki
Nanae
N
Kada
Atsushi
A
Ishihara
Keiko
K
Kawai-Kowase
Takayoshi
T
Matsumura
Kana
K
Sasaki
Yoshiko
Y
Munemasa
Ichiro
I
Manabe
Masahiko
M
Kurabayashi
Tucker
T
Collins
Ryozo
R
Nagai
D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008156:Luciferases / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D016335:Zinc Fingers
D017931:DNA Primers; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D021122:Protein Subunits; D011994:Recombinant Proteins; D015534:Trans-Activators; C075278:platelet-derived growth factor A; D008156:Luciferases