1. Differential Effects on ARF Stability by Normal versus Oncogenic Levels of c-Myc Expression.
- Author
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Chen, Delin, Kon, Ning, Zhong, Jiayun, Zhang, Pingzhao, Yu, Long, and Gu, Wei
- Subjects
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ADP-ribosylation factors , *MYC oncogenes , *GENE expression , *GROWTH factors , *TUMOR proteins , *CELL proliferation - Abstract
Summary: 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. [Copyright &y& Elsevier]
- Published
- 2013
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