Gregory Mark A, Qi Ying, Hann Stephen R
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2175, USA.
Cell Cycle. 2005 Feb;4(2):249-52. Epub 2005 Feb 21.
The ARF tumor suppressor protein acts in a checkpoint that guards against unscheduled cellular proliferation in response to oncogenic signaling. Deregulated expression of c-Myc induces ARF expression and apoptosis through the ARF-Mdm2-p53 axis. Our recent study reveals a new direct role for ARF in controlling c-Myc's oncogenic activity that is independent of p53. ARF binds to and selectively impairs the transactivation ability of c-Myc while leaving its transrepression ability intact. Biologically, ARF prevents hyper-proliferation and transformation caused by c-Myc and enhances c-Myc-induced apoptosis independently of p53. These new findings may be especially relevant for therapeutic strategies targeting c-Myc-induced cancers.
ARF肿瘤抑制蛋白在一个检查点中发挥作用，该检查点可防止细胞因致癌信号而发生异常增殖。c-Myc的失调表达通过ARF-Mdm2-p53轴诱导ARF表达和凋亡。我们最近的研究揭示了ARF在控制c-Myc致癌活性方面的一种新的直接作用，这种作用独立于p53。ARF与c-Myc结合并选择性地损害其反式激活能力，同时保持其反式抑制能力不变。在生物学上，ARF可防止c-Myc引起的过度增殖和转化，并独立于p53增强c-Myc诱导的凋亡。这些新发现可能与针对c-Myc诱导的癌症的治疗策略特别相关。
