TY - JOUR
T1 - Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit
AU - Takeuchi, Yoshinori
AU - Yahagi, Naoya
AU - Izumida, Yoshihiko
AU - Nishi, Makiko
AU - Kubota, Midori
AU - Teraoka, Yuji
AU - Yamamoto, Takashi
AU - Matsuzaka, Takashi
AU - Nakagawa, Yoshimi
AU - Sekiya, Motohiro
AU - Iizuka, Yoko
AU - Ohashi, Ken
AU - Osuga, Jun Ichi
AU - Gotoda, Takanari
AU - Ishibashi, Shun
AU - Itaka, Keiji
AU - Kataoka, Kazunori
AU - Nagai, Ryozo
AU - Yamada, Nobuhiro
AU - Kadowaki, Takashi
AU - Shimano, Hitoshi
PY - 2010/4/9
Y1 - 2010/4/9
N2 - Sterol regulatory element-binding protein (SREBP)-1 is a key transcription factor for the regulation of lipogenic enzyme genes in the liver. Polyunsaturated fatty acids (PUFA) selectively suppress hepatic SREBP-1, but molecular mechanisms remain largely unknown. To gain insight into this regulation, we established in vivo reporter assays to assess the activities of Srebf1c transcription and proteolytic processing. Using these in vivo reporter assays, we showed that the primary mechanism for PUFA suppression of SREBP-1 is at the proteolytic processing level and that this suppression in turn decreases the mRNA transcription through lowering SREBP-1 binding to the SREBP-binding element on the promoter ("autoloop regulatory circuit"), although liver X receptor, an activator for Srebf1c transcription, is not involved in this regulation by PUFA. The mechanisms forPUFAsuppression of SREBP-1 confirm that the autoloop regulation for transcription is crucial for the nutritional regulation of triglyceride synthesis.
AB - Sterol regulatory element-binding protein (SREBP)-1 is a key transcription factor for the regulation of lipogenic enzyme genes in the liver. Polyunsaturated fatty acids (PUFA) selectively suppress hepatic SREBP-1, but molecular mechanisms remain largely unknown. To gain insight into this regulation, we established in vivo reporter assays to assess the activities of Srebf1c transcription and proteolytic processing. Using these in vivo reporter assays, we showed that the primary mechanism for PUFA suppression of SREBP-1 is at the proteolytic processing level and that this suppression in turn decreases the mRNA transcription through lowering SREBP-1 binding to the SREBP-binding element on the promoter ("autoloop regulatory circuit"), although liver X receptor, an activator for Srebf1c transcription, is not involved in this regulation by PUFA. The mechanisms forPUFAsuppression of SREBP-1 confirm that the autoloop regulation for transcription is crucial for the nutritional regulation of triglyceride synthesis.
UR - http://www.scopus.com/inward/record.url?scp=77951218102&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.096107
DO - 10.1074/jbc.M109.096107
M3 - 学術論文
C2 - 20145241
AN - SCOPUS:77951218102
SN - 0021-9258
VL - 285
SP - 11681
EP - 11691
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 15
ER -