Major intestinal coactivator p300 strongly activates peroxisome proliferator-activated receptor in intestinal cell line, Caco-2.
We have previously reported that several genes related to intestinal fatty acid and vitamin A metabolism are coordinately regulated by peroxisome proliferator-activated receptor (PPAR) [Arch. Biochem. Biophys. 389 (2001) 41; Biochim. Biophys. Acta 1531 (2001) 68]. In this study, we demonstrated that PPAR alpha and PPAR delta interacted with endogenous coactivators in intestinal cell line, Caco-2 in a ligand specific manner. We isolated rat cDNA clones encoding the nuclear receptor interaction domains of the two transcriptional coactivators, CREB-binding protein (CBP) and p300. Expression level of CBP mRNA was relatively low in the small intestine, while p300 mRNA was ubiquitously expressed in various tissues including the small intestine in the rat. Southern blot analysis revealed that these coactivators were encoded by different genes. Mammalian two-hybrid assays in Caco-2 cells revealed that p300 interacted with PPAR alpha or PPAR delta in the presence of their specific ligands more efficiently than CBP did. These results suggest that the major intestinal coactivator, p300 strongly interacts with PPAR alpha and PPAR delta.
Mochizuki
Kazuki
K
Department of Nutrition, School of Food and Nutritional Sciences, The University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Suruga
Kazuhito
K
Sakaguchi
Naomi
N
Takase
Sachiko
S
Goda
Toshinao
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D050882:CREB-Binding Protein; D018938:Caco-2 Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D050881:E1A-Associated p300 Protein; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
D018076:DNA, Complementary; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C494365:Crebbp protein, rat; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat