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Publication : NUCKS is a positive transcriptional regulator of insulin signaling.

First Author  Qiu B Year  2014
Journal  Cell Rep Volume  7
Issue  6 Pages  1876-86
PubMed ID  24931609 Mgi Jnum  J:211777
Mgi Id  MGI:5576396 Doi  10.1016/j.celrep.2014.05.030
Citation  Qiu B, et al. (2014) NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling. Cell Rep 7(6):1876-86
abstractText  Although much is known about the molecular players in insulin signaling, there is scant information about transcriptional regulation of its key components. We now find that NUCKS is a transcriptional regulator of the insulin signaling components, including the insulin receptor (IR). Knockdown of NUCKS leads to impaired insulin signaling in endocrine cells. NUCKS knockout mice exhibit decreased insulin signaling and increased body weight/fat mass along with impaired glucose tolerance and reduced insulin sensitivity, all of which are further exacerbated by a high-fat diet (HFD). Genome-wide ChIP-seq identifies metabolism and insulin signaling as NUCKS targets. Importantly, NUCKS is downregulated in individuals with a high body mass index and in HFD-fed mice, and conversely, its levels increase upon starvation. Altogether, NUCKS is a physiological regulator of energy homeostasis and glucose metabolism that works by regulating chromatin accessibility and RNA polymerase II recruitment to the promoters of IR and other insulin pathway modulators.
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