We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

A RA-dependent, tumour-growth suppressive transcription complex is the target of the PML-RARalpha and T18 oncoproteins.

Nature genetics | Nov 7, 1999

PML and Tif1a are fused to RARA and Braf, respectively, resulting in the production of PML-RARalpha and Tif1alpha-B-Raf (T18) oncoproteins. Here we show that PML, Tif1alpha and RXRalpha/RARalpha function together in a transcription complex that is dependent on retinoic acid (RA). We found that PML acts as a ligand-dependent coactivator of RXRalpha/RARalpha. PML interacts with Tif1alpha and CBP. In Pml-/- cells, the RA-dependent induction of genes such as RARB2 and the ability of Tif1alpha and CBP to act as transcriptional coactivators on RA are impaired. We show that both PML and Tif1alpha are growth suppressors required for the growth-inhibitory activity of RA. T18, similar to PML-RARalpha, 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).

Pubmed ID: 10610177 RIS Download

Mesh terms: Animals | CREB-Binding Protein | Cell Differentiation | Cell Division | Cell Line | Cell Nucleus | Cell Transformation, Neoplastic | DNA | Gene Expression Regulation, Neoplastic | Genes, Tumor Suppressor | Humans | Leukemia, Promyelocytic, Acute | Mutation | Neoplasm Proteins | Nuclear Proteins | Oncogene Proteins, Fusion | Promoter Regions, Genetic | Protein Binding | Protein Isoforms | Receptors, Retinoic Acid | Retinoid X Receptors | Trans-Activators | Transcription Factors | Transfection | Tretinoin

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA-08748
  • Agency: NCI NIH HHS, Id: CA71692
  • Agency: NCI NIH HHS, Id: CA74031

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.