In vivo stabilization of nuclear retinoid X receptor alpha in the presence of peroxisome proliferator-activated receptor alpha.
Retinoid X receptor alpha (RXRalpha) can reveal diverse functions through forming a heterodimer with peroxisome proliferator-activated receptor alpha (PPARalpha). However, the mechanism of regulation of the cellular RXRalpha level is unclear. Thus, quantitative change of RXRalpha was investigated in mouse liver. Nuclear RXRalpha level was constitutively lower in PPARalpha-null mice than in wild-type mice. The level was also increased by clofibrate treatment in wild-type mice without a concomitant increase of RXRalpha mRNA, but not in PPARalpha-null mice. Pulse chase experiments demonstrated that the presence of PPARalpha and its activation by ligands significantly affected the stability of nuclear RXRalpha. These findings suggest a novel regulatory mechanism of nuclear RXRalpha in vivo.
Tanaka
Naoki
N
Department of Aging Biochemistry, Research Center on Aging and Adaptation, Shinshu University School of Medicine, 3-1-1 Asahi, 390-8621, Matsumoto, Japan.
Hora
Kazuhiko
K
Makishima
Hideki
H
Kamijo
Yuji
Y
Kiyosawa
Kendo
K
Gonzalez
Frank J
FJ
Aoyama
Toshifumi
T
D000818:Animals; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D009687:Nuclear Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors