Horm Metab Res 2002; 34(6): 303-310
DOI: 10.1055/s-2002-33258
Original Basic
© Georg Thieme Verlag Stuttgart · New York

APE/Ref-1 is Controlled by Both Redox and cAMP-Dependent Mechanisms in Rat Thyroid Cells

G.  Tell 2 , A.  Pines 2 , M.  Pandolfi 3 , A.  V.  D’Elia 1 , D.  Donnini 1 , R.  Lonigro 1 , G.  Manzini 2 , D.  Russo 4 , C.  Di Loreto 3 , G.  Damante 1
  • 1Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine. M.A.T.I. Center.
  • 2Dipartimento di Biochimica Biofisica e Chimica delle Macromolecole, Università di Trieste, C.E.B.
  • 3Dipartimento di Ricerche Mediche e Morfologiche, Università di Udine.
  • 4Dipartimento di Scienze Farmacobiologiche, Università di Catanzaro
Further Information

Publication History

Received 26 July 2001

Accepted after Revision 12 February 2002

Publication Date:
12 August 2002 (online)

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Abstract

APE/Ref-1 is a multifunctional protein possessing both redox and DNA repair functions. Through its redox activity, APE/Ref-1 controls the DNA-binding function of several transcriptional regulators (AP1, NF-κB, p53, Pax proteins). We have previously shown that APE/Ref-1 upregulates the transcriptional activity of the thyroid-specific transcription factor Pax8. In thyroid cells, APE/Ref-1 can be detected both in the nuclear and cytoplasmatic compartments. In this study regulatory mechanisms acting on APE/Ref-1 were revealed using the FRTL-5 cell line. TSH induces both cytoplasm-to-nucleus translocation and neosynthesis of APE/Ref-1 protein. Interestingly, only neosynthesis is dependent on cAMP signalling. In contrast, the cytoplasm-to-nucleus translocation is dependent on redox-mediated mechanisms. Based upon the data shown in this study and in others, a bimodal control of APE/Ref-1 by TSH can be delineated.