HMGA1 is a novel downstream nuclear target of the insulin receptor signaling pathway.

Scientific Reports
Eusebio ChiefariAntonio Brunetti

Abstract

High-mobility group AT-hook 1 (HMGA1) protein is an important nuclear factor that activates gene transcription by binding to AT-rich sequences in the promoter region of DNA. We previously demonstrated that HMGA1 is a key regulator of the insulin receptor (INSR) gene and individuals with defects in HMGA1 have decreased INSR expression and increased susceptibility to type 2 diabetes mellitus. In addition, there is evidence that intracellular regulatory molecules that are employed by the INSR signaling system are involved in post-translational modifications of HMGA1, including protein phosphorylation. It is known that phosphorylation of HMGA1 reduces DNA-binding affinity and transcriptional activation. In the present study, we investigated whether activation of the INSR by insulin affected HMGA1 protein phosphorylation and its regulation of gene transcription. Collectively, our findings indicate that HMGA1 is a novel downstream target of the INSR signaling pathway, thus representing a new critical nuclear mediator of insulin action and function.

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Citations

Apr 27, 2013·Naunyn-Schmiedeberg's Archives of Pharmacology·Wei ChenLili Wang
Apr 5, 2013·Immunological Reviews·Joan Yuan, Stefan A Muljo
Sep 21, 2013·International Journal of Molecular Sciences·Amaresh C PandaKotb Abdelmohsen
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Feb 2, 2018·Frontiers in Endocrinology·Salvatore De RosaDaniela P Foti
Oct 11, 2017·World Journal of Diabetes·Biagio ArcidiaconoAntonio Brunetti
Oct 4, 2017·Endocrine Reviews·Antonino BelfioreRiccardo Vigneri
Jan 23, 2020·International Journal of Molecular Sciences·Robert Vignali, Silvia Marracci
Oct 21, 2017·Endocrine·Biagio ArcidiaconoAntonio Brunetti
Jun 6, 2018·Scientific Reports·Eusebio ChiefariAntonio Brunetti
Jun 30, 2015·Biomolecules·Arndt G Benecke, Sebastian Eilebrecht
Jul 24, 2018·Frontiers in Endocrinology·Eusebio ChiefariAntonio Brunetti
Dec 22, 2020·The Journal of Molecular Diagnostics : JMD·Xiu Q WangTorsten O Nielsen
Apr 28, 2020·The Korean Journal of Internal Medicine·Kyu-Sun LeeWoo Jin Kim
Sep 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Catalina A PomarJuana Sánchez
Nov 14, 2021·Cellular and Molecular Life Sciences : CMLS·Weiwei Liu, Guokai Chen

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Methods Mentioned

BETA
acetylation
immunoprecipitation
ChIP
electrophoretic mobility shift assay
transfection
PCR

Software Mentioned

Data Analysis

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