| First Author | Tisserand J | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 38 | Pages | 33369-79 |
| PubMed ID | 21768647 | Mgi Jnum | J:356311 |
| Mgi Id | MGI:7762403 | Doi | 10.1074/jbc.M111.225680 |
| Citation | Tisserand J, et al. (2011) Tripartite motif 24 (Trim24/Tif1alpha) 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 alpha (Raralpha) inhibition. J Biol Chem 286(38):33369-79 |
| abstractText | Recent genetic studies in mice have established that the nuclear receptor coregulator Trim24/Tif1alpha suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor alpha (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. |
