title: HMGA1 is a novel downstream nuclear target of the insulin receptor signaling pathway.
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.
authors.forename: Eusebio
authors.initials: E
authors.lastname: Chiefari
authors.forename: Maria T
authors.initials: MT
authors.lastname: Nevolo
authors.forename: Biagio
authors.initials: B
authors.lastname: Arcidiacono
authors.forename: Elisa
authors.initials: E
authors.lastname: Maurizio
authors.forename: Aurora
authors.initials: A
authors.lastname: Nocera
authors.forename: Stefania
authors.initials: S
authors.lastname: Iiritano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sgarra
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Possidente
authors.forename: Camillo
authors.initials: C
authors.lastname: Palmieri
authors.forename: Francesco
authors.initials: F
authors.lastname: Paonessa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Brunetti
authors.forename: Guidalberto
authors.initials: G
authors.lastname: Manfioletti
authors.forename: Daniela
authors.initials: D
authors.lastname: Foti
authors.forename: Antonio
authors.initials: A
authors.lastname: Brunetti