APE/Ref-1 is controlled by both redox and cAMP-dependent mechanisms in rat thyroid cells.
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-kappaB, 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.
Tell
G
G
Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine. M.A.T.I. Center, Udine, Italy.
Pines
A
A
Pandolfi
M
M
D'Elia
A V
AV
Donnini
D
D
Lonigro
R
R
Manzini
G
G
Russo
D
D
Di Loreto
C
C
Damante
G
G
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D019757:Carbon-Oxygen Lyases / Q000032:analysis* / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D010084:Oxidation-Reduction; D051381:Rats; D015398:Signal Transduction; D013961:Thyroid Gland / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D013972:Thyrotropin / Q000494:pharmacology*
D013972:Thyrotropin; D000242:Cyclic AMP; D019757:Carbon-Oxygen Lyases; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D002118:Calcium