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

Sci Rep 2012 7;2:251. Epub 2012 Feb 7.

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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http://dx.doi.org/10.1038/srep00251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273854PMC
September 2012
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References

(Supplied by CrossRef)

M Bustin et al.
Prog. Nucleic Acids Res. 1996

R Reeves et al.
Gene 2001

D Thanos et al.
Cell 1995

SA OƱate et al.
Mol. Cell. Biol. 1994

JV Falvo et al.
Cell 1995

R Reeves et al.
Prog. Cell Cycle Res. 1995

JR Huth et al.
Nat. Struct. Biol. 1997

DD Edberg et al.
Biochemistry 2004

R Sgarra et al.
J. Proteome Res. 2009

D-Z Wang et al.
J. Biol. Chem. 1995

A Brunetti et al.
FASEB J. 2001

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