c-MYC protein is degraded in response to UV irradiation
c-MYC protein is degraded in response to UV irradiation
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DOI：
10.4161/cc.7.1.5111
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发表时间：
2008-01-01
期刊：
影响因子：
4.3
通讯作者：
Calsou, Patrick
中科院分区：
文献类型：
--
作者：
Britton, Sebastien;Salles, Bernard;Calsou, Patrick
c-MYC原癌基因编码一种对细胞生长和增殖至关重要的转录因子。它是癌细胞中经常改变的基因之一，在癌细胞中它表现出组成性活性。由于泛素介导的蛋白水解，c-MYC在静止细胞中的半衰期非常短。我们在这里报告的快速和剂量依赖性下降的c-MYC蛋白水平紫外线照射后，在各种人类和啮齿动物细胞。这种下降是由于c-MYC蛋白的蛋白酶体降解，并且不需要FBW 7和SKP 2泛素连接酶的结合位点。总之，我们的数据排除了应激反应激酶PAK 2，主要的磷酸肌醇3-激酶相关的蛋白激酶ATR，ATM，DNA-PK和mTOR和ERK，JNK和p38丝裂原活化蛋白激酶在这个UV诱导的降解过程中的突出作用。我们认为，c-MYC降解是全球细胞对紫外线损伤反应的一部分，与p53转录因子的积累和激活互补。通过在对基因组造成损伤后促进复制停滞，c-MYC的诱导降解可能是维持基因组稳定性的保障机制的一部分。
The c-MYC proto-oncogene encodes a transcription factor that is critical for cell growth and proliferation. It is one of the genes frequently altered in cancer cells in which it exhibits constitutive activity. The half-life of c-MYC is very short in quiescent cells due to ubiquitin-mediated proteolysis. We report here the rapid and dose-dependent decline of c-MYC protein level after UV-irradiation in various human and rodent cells. This decline is due to a proteasomal degradation of c-MYC protein and does not require the binding sites for the FBW7 and SKP2 ubiquitin ligases. Together, our data exclude a prominent role for the stress-responsive kinase PAK2, for the major phosphoinositide 3-kinase related protein kinases ATR, ATM, DNA-PK and mTOR and for ERK, JNK and p38 mitogen activated protein kinases in this UV-induced degradation process. We propose that c-MYC degradation is part of the global cell response to UV-damage, complementary to the accumulation and activation of the p53 transcription factor. By contributing to the replication arrest after infliction of lesions to the genome, the induced degradation of c-MYC may be part of the safeguard mechanisms maintaining genome stability.