Cell cycle control by the thyroid hormone in neuroblastoma cells.
The 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.
Garcia-Silva
Susana
S
Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid, Spain.
Perez-Juste
German
G
Aranda
Ana
A
D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D019940:Genes, bcl-1 / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D009447:Neuroblastoma / Q000473:pathology*; D009474:Neurons / Q000187:drug effects; D011233:Precipitin Tests; D012313:RNA / Q000096:biosynthesis / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016160:Retinoblastoma Protein; D014284:Triiodothyronine; D012313:RNA