title: Retinoblastoma protein acts as Pax 8 transcriptional coactivator.
abstract: Control of cell proliferation and differentiation by the retinoblastoma protein (pRb) depends on its interactions with key cellular substrates. Available data indicate that pRb and the transcription factor Pax 8 play a crucial role in the differentiation of thyroid follicular cells. In this study, we show that pRb takes part in the complex assembled on the thyroperoxidase gene promoter acting as a transcriptional coactivator of Pax 8. Accordingly, pRb interacts with and potentiates Pax 8 transcriptional activity. In addition, we show that the downregulation of pRb gene expression, in thyrocytes, through RNA interference results in a reduction of the thyroperoxidase gene promoter activity mediated by the Pax 8-binding site. In agreement with these results and with the ability of the adenoviral protein E1A to bind pRb, we show that E1A downregulates Pax 8 activity and that such inhibition requires the E1A-Rb interaction. Furthermore, we show that the Pax 8/pRb synergy plays a role on the sodium/iodide symporter gene expression as well.
authors: Molecular Pathology Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy.
authors: Stefania
authors: S
authors: Miccadei
authors: Claudia
authors: C
authors: Provenzano
authors: Martin
authors: M
authors: Mojzisek
authors: Pier Giorgio
authors: PG
authors: Natali
authors: Donato
authors: D
authors: Civitareale
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism; D001665:Binding Sites; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D025941:Protein Interaction Mapping; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D000099209:Sodium-Iodide Symporters
chemical_list: D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D005982:Glutathione Transferase; D007453:Iodide Peroxidase; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D027981:Symporters; D015534:Trans-Activators; D000099209:Sodium-Iodide Symporters; C083325:PAX8 protein, human