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	Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology
	York, Brian（Baylor Coll Med, Dept Mol & Cellular Biol） ; Yu, Chundong ; Yu CD(俞春东) ; Sagen, Jorn V.（Baylor Coll Med, Dept Mol & Cellular Biol） ; Liu, Zhaoliang（Baylor Coll Med, Dept Mol & Cellular Biol） ; Nikolai, Bryan C.（Baylor Coll Med, Dept Mol & Cellular Biol） ; Wu, Ray-Chang（Baylor Coll Med, Dept Mol & Cellular Biol） ; Xu, Jianming（Baylor Coll Med, Dept Mol & Cellular Biol） ; O'Malley, Bert W.（Baylor Coll Med, Dept Mol & Cellular Biol） ; Sagen, Jorn V.（Univ Bergen, Inst Med） ; Finegold, Milton（ Baylor Coll Med）
	2010-06-15
关键词	coactivator metabolism posttranslational modification obesity
英文摘要	Here we demonstrate that reprogramming steroid receptor coactivator-3 (SRC-3) function by changing its posttranslational modification (PTM) code drastically influences systems biology. These findings support the physiological importance of PTMs in directing in vivo functions of a master coregulator. We previously reported that the transactivation potential of SRC-3 is controlled in part by PTMs, although this data emanated from in vitro studies. To test the physiological implications of PTMs on SRC-3, we developed a knock-in mouse model containing mutations at four conserved phosphorylation sites. These mice displayed a systems biology phenotype with increased body weight and adiposity, coupled with reduced peripheral insulin sensitivity. Collectively, these phenotypes result from increased IGF1 signaling, due to elevated IGFBP3 levels. We provide convincing evidence that these mutations in SRC-3 promoted enhanced transcription of the IGFBP3 gene and globally influenced growth and metabolism. Consequently, these mice displayed increased liver tumorigenesis, which likely results from elevated IGF1 signaling.; Norwegian Cancer Society ; University of Bergen ; Det regionale samarbeidsorganet ; Norwegian Society of Endocrinology ; NIH [R01 DK058242, R01 CA112403]; Susan G. Komen [BCTR0707225]; National Institutes of Health (NIH)-DDC Core Morphology Lab [DK56338]; Nuclear Receptor Signaling Atlas/NIDDK [U19 DK62434-08]; NIDDK [P01 HD8818-37]
语种	英语
出版者	NATL ACAD SCIENCES
内容类型	期刊论文
源URL	[http://dx.doi.org/doi:10.1073/pnas.1005262107]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	York, Brian,Yu, Chundong,Yu CD,et al. Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology[J],2010.
APA	York, Brian.,Yu, Chundong.,俞春东.,Sagen, Jorn V..,Liu, Zhaoliang.,...&Finegold, Milton.(2010).Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology..
MLA	York, Brian,et al."Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology".(2010).

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