Involvement of CREB-regulated transcription coactivators (CRTC) in transcriptional activation of steroidogenic acute regulatory protein (Star) by ACTH - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue Molecular and Cellular Endocrinology Année : 2020

Involvement of CREB-regulated transcription coactivators (CRTC) in transcriptional activation of steroidogenic acute regulatory protein (Star) by ACTH

Lorna I.F. Smith
  • Fonction : Auteur
Victoria Huang
  • Fonction : Auteur
Mark Olah
  • Fonction : Auteur
Loc Trinh
  • Fonction : Auteur
Ying Liu
Becky Conway-Campbell
  • Fonction : Auteur
Zidong Zhao
  • Fonction : Auteur
Stafford Lightman
Francesca Spiga
  • Fonction : Auteur
Greti Aguilera
  • Fonction : Auteur

Résumé

Studies in vivo have suggested the involvement of CREB-regulated transcription coactivator (CRTC)2 on ACTHinduced transcription of the key steroidogenic protein, Steroidogenic Acute Regulatory (StAR). The present study uses two ACTH-responsive adrenocortical cell lines, to examine the role of CRTC on Star transcription. Here we show that ACTH-induced Star primary transcript, or heteronuclear RNA (hnRNA), parallels rapid increases in nuclear levels of the 3 isoforms of CRTC; CRTC1, CRTC2 and CRTC3. Furthermore, ACTH promotes recruitment of CRTC2 and CRTC3 by the Star promoter and siRNA knockdown of either CRTC3 or CRTC2 attenuates the increases in ACTH-induced Star hnRNA. Using pharmacological inhibitors of PKA, MAP kinase and calcineurin, we show that the effects of ACTH on Star transcription and CRTC nuclear translocation depend predominantly on the PKA pathway. The data provides evidence that CRTC2 and CRTC3, contribute to activation of Star transcription by ACTH, and that PKA/CRTC-dependent pathways are part of the multifactorial mechanisms regulating Star transcription.
Fichier principal
Vignette du fichier
Smith et al.2020.pdf (1.9 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03060153 , version 1 (21-12-2020)

Identifiants

Citer

Lorna I.F. Smith, Victoria Huang, Mark Olah, Loc Trinh, Ying Liu, et al.. Involvement of CREB-regulated transcription coactivators (CRTC) in transcriptional activation of steroidogenic acute regulatory protein (Star) by ACTH. Molecular and Cellular Endocrinology, 2020, 499, pp.110612. ⟨10.1016/j.mce.2019.110612⟩. ⟨hal-03060153⟩
102 Consultations
90 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More