| First Author | Lessard F | Year | 2010 |
| Journal | Mol Cell | Volume | 38 |
| Issue | 4 | Pages | 539-50 |
| PubMed ID | 20513429 | Mgi Jnum | J:162926 |
| Mgi Id | MGI:4820652 | Doi | 10.1016/j.molcel.2010.03.015 |
| Citation | Lessard F, et al. (2010) The ARF tumor suppressor controls ribosome biogenesis by regulating the RNA polymerase I transcription factor TTF-I. Mol Cell 38(4):539-50 |
| abstractText | The p14/p19(ARF) (ARF) product of the CDKN2A gene displays tumor suppressor activity both in the presence and absence of p53/TP53. In p53-negative cells, ARF arrests cell proliferation, at least in part, by suppressing ribosomal RNA synthesis. We show that ARF does this by controlling the subnuclear localization of the RNA polymerase I transcription termination factor, TTF-I. TTF-I shuttles between nucleoplasm and nucleolus with the aid of the chaperone NPM/B23 and a nucleolar localization sequence within its N-terminal regulatory domain. ARF inhibits nucleolar import of TTF-I by binding to this nucleolar localization sequence, causing the accumulation of TTF-I in the nucleoplasm. Depletion of TTF-I recapitulates the effects of ARF on ribosomal RNA synthesis and is rescued by the introduction of a TTF-I transgene. Thus, our data delineate the pathway by which ARF regulates ribosomal RNA synthesis and provide a compelling explanation for the role of NPM. |
