The Journal of biological chemistry, 2011-09, Vol.286 (38), p.33369-33379
2011
Details
- Autor(en) / Beteiligte
- Titel
- Tripartite Motif 24 (Trim24/Tif1α) Tumor Suppressor Protein Is a Novel Negative Regulator of Interferon (IFN)/Signal Transducers and Activators of Transcription (STAT) Signaling Pathway Acting through Retinoic Acid Receptor α (Rarα) Inhibition
- Ist Teil von
- The Journal of biological chemistry, 2011-09, Vol.286 (38), p.33369-33379
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Recent genetic studies in mice have established that the nuclear receptor coregulator Trim24/Tif1α suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor α (Rara)-dependent transcription and cell proliferation. However, Rara targets regulated by Trim24 remain unknown. We report that the loss of Trim24 resulted in interferon (IFN)/STAT pathway overactivation soon after birth (week 5). Despite a transient attenuation of this pathway by the induction of several IFN/STAT pathway repressors later in the disease, this phenomenon became more pronounced in tumors. Remarkably, Rara haplodeficiency, which suppresses tumorigenesis in Trim24−/− mice, prevented IFN/STAT overactivation. Moreover, together with Rara, Trim24 bound to the retinoic acid-responsive element of the Stat1 promoter and repressed its retinoic acid-induced transcription. Altogether, these results identify Trim24 as a novel negative regulator of the IFN/STAT pathway and suggest that this repression through Rara inhibition may prevent liver cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9258eISSN: 1083-351XDOI: 10.1074/jbc.M111.225680Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3190892
- Format
- –
- Schlagworte
- Animals, Carcinoma, Hepatocellular - genetics, Cluster Analysis, Gene Dosage, Gene Expression Regulation - drug effects, Humans, Interferons - metabolism, Liver, Liver - drug effects, Liver - metabolism, Liver Neoplasms - genetics, Liver Tumorigenesis, Mice, Microarray, Models, Biological, Molecular Bases of Disease, Nuclear Proteins - deficiency, Nuclear Proteins - metabolism, Nuclear Receptors, Receptors, Retinoic Acid - antagonists & inhibitors, Receptors, Retinoic Acid - metabolism, Reproducibility of Results, Retinoic Acid, Retinoic Acid Receptor alpha, Signal Transduction - drug effects, Signal Transduction - genetics, STAT Transcription Factors - metabolism, Stat1, Transcription, Transcription Factors - deficiency, Transcription Factors - metabolism, Transcriptome, Tretinoin - pharmacology, Trim24 (Tif1α), Tumor