Garcia-Silva, SusanaPerez-Juste, GermanAranda, Ana2026-02-202026-02-202002-12-27Toxicology . 2002 Dec 27:181-182:179-82.https://hdl.handle.net/20.500.12105/27242The thyroid hormone (T3) blocks proliferation and induces differentiation of neuroblastoma N2a-beta cells that overexpress the beta 1 isoform of the T3 receptor. An element in the region responsible for premature termination of transcription mediates a rapid repression of c-myc gene expression by T3. The hormone also causes a decrease of cyclin D1 gene transcription, and is able to antagonize the activation of the cyclin D1 promoter by Ras. In addition, a strong and sustained increase of the levels of the cyclin kinase inhibitor (CKI) p27(Kip1) are found in T3-treated cells. The increased levels of p27(Kip1) lead to a marked inhibition of the kinase activity of the cyclin-CDK2 complexes. As a consequence of these changes, retinoblastoma proteins are hypophosphorylated in T3-treated N2a-beta cells, and progression through the restriction point in the cell cycle is blocked.engthyroid hormonecell cyclec-myccyclin D1p27Kip1cyclin-dependent kinase-2research article12505306181182179-182TOXICOLOGYopen access