| First Author | Rounbehler RJ | Year | 2012 |
| Journal | Cell | Volume | 150 |
| Issue | 3 | Pages | 563-74 |
| PubMed ID | 22863009 | Mgi Jnum | J:187885 |
| Mgi Id | MGI:5438689 | Doi | 10.1016/j.cell.2012.06.033 |
| Citation | Rounbehler RJ, et al. (2012) Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state. Cell 150(3):563-74 |
| abstractText | Myc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis. |
