A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARα and T18 oncoproteins Journal Article
| Authors: | Zhong, S.; Delva, L.; Rachez, C.; Cenciarelli, C.; Gandini, D.; Zhang, H.; Kalantry, S.; Freedman, L. P.; Pandolfi, P. P. |
| Article Title: | A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARα and T18 oncoproteins |
| Abstract: | PML and Tif1a are fused to RARA and Braf, respectively, resulting in the production of PML-RARα and Tif1α-B-Raf (T18) oncoproteins. Here we show that PML, Tif1α and RXRα/RARα function together in a transcription complex that is dependent on retinoic acid (RA). We found that PML acts as a ligand- dependent coactivator of RXRα/RARα. PML interacts with Tif1α and CBP. In Pml(-/-) cells, the RA-dependent induction of genes such as RARB2 and the ability of Tif1α and CBP to act as transcriptional coactivators on RA are impaired. We show that both PML and Tif1α are growth suppressors required for the growth-inhibitory activity of RA. T18, similar to PML-RARα, disrupts the RA-dependent activity of this complex in a dominant-negative manner resulting in a growth advantage. Our data define a new pathway for the control of cell growth and tumorigenesis, and provide a new model for the pathogenesis of acute promyelocytic leukaemia (APL). |
| Keywords: | oncoprotein; mutation; nonhuman; protein analysis; animal cell; animals; cell division; cell growth; protein protein interaction; neoplasm proteins; cell line; protein binding; cell differentiation; transfection; cancer model; carcinogenesis; animalia; transcription factors; cell transformation, neoplastic; nuclear proteins; leukemia, promyelocytic, acute; gene expression regulation, neoplastic; dna; transcription regulation; leukemogenesis; acute myeloblastic leukemia; oncogene proteins, fusion; trans-activators; cell nucleus; gene induction; tumor growth; retinoic acid; protein isoforms; genes, tumor suppressor; growth inhibition; tretinoin; receptors, retinoic acid; promoter regions (genetics); creb-binding protein; retinoid x receptor; retinoid x receptors; humans; priority journal; article |
| Journal Title: | Nature Genetics |
| Volume: | 23 |
| Issue: | 3 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1999-11-01 |
| Start Page: | 287 |
| End Page: | 295 |
| Language: | English |
| DOI: | 10.1038/15463 |
| PUBMED: | 10610177 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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