| First Author | Chen D | Year | 2013 |
| Journal | Mol Cell | Volume | 51 |
| Issue | 1 | Pages | 46-56 |
| PubMed ID | 23747016 | Mgi Jnum | J:199251 |
| Mgi Id | MGI:5501373 | Doi | 10.1016/j.molcel.2013.05.006 |
| Citation | Chen D, et al. (2013) Differential Effects on ARF Stability by Normal versus Oncogenic Levels of c-Myc Expression. Mol Cell 51(1):46-56 |
| abstractText | ARF suppresses aberrant cell growth upon c-Myc overexpression by activating p53 responses. Nevertheless, the precise mechanism by which ARF specifically restrains the oncogenic potential of c-Myc without affecting its normal physiological function is not well understood. Here, we show that low levels of c-Myc expression stimulate cell proliferation, whereas high levels inhibit by activating the ARF/p53 response. Although the mRNA levels of ARF are induced in both scenarios, the accumulation of ARF protein occurs only when ULF-mediated degradation of ARF is inhibited by c-Myc overexpression. Moreover, the levels of ARF are reduced through ULF-mediated ubiquitination upon DNA damage. Blocking ARF degradation by c-Myc overexpression dramatically stimulates the apoptotic responses. Our study reveals that ARF stability control is crucial for differentiating normal (low) versus oncogenic (high) levels of c-Myc expression and suggests that differential effects on ULF- mediated ARF ubiquitination by c-Myc levels act as a barrier in oncogene-induced stress responses. |
