Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, 55912, USA.
Oncogene. 2012 Apr 5;31(14):1835-44. doi: 10.1038/onc.2011.369. Epub 2011 Aug 22.
The c-Jun transcription factor is a highly unstable oncoprotein. Several ubiquitin ligases mediate c-Jun degradation. However, c-Jun can be stabilized once it is phosphorylated at the N-terminus by c-Jun N-terminal kinases (JNKs) or other protein kinases. This phosphorylation decreases c-Jun ubiquitination and degradation. The underlying mechanism for this phenomenon is still unknown. Here, we show that receptor for activated C-kinase 1 (Rack1) can bind with c-Jun and ubiquitin ligase Fbw7 to form a complex. When c-Jun is phosphorylated at the N-terminus, c-Jun is released from the complex and cannot be ubiquitinated by Fbw7, which leads to increased stabilization and accumulation of c-Jun. These results reveal that Rack1 has a very important role in tumorigenesis by maintaining the stability of c-Jun that has been phosphorylated at its N-terminus by JNKs or other kinases.
c-Jun 转录因子是一种极不稳定的癌蛋白。几种泛素连接酶介导 c-Jun 的降解。然而，一旦 c-Jun 的 N 端被 c-Jun N 端激酶（JNK）或其他蛋白激酶磷酸化，它就可以稳定下来。这种磷酸化降低了 c-Jun 的泛素化和降解。这一现象的潜在机制尚不清楚。在这里，我们表明，激活的 C 激酶 1（Rack1）受体可以与 c-Jun 和泛素连接酶 Fbw7 结合形成复合物。当 c-Jun 的 N 端被磷酸化时，c-Jun 从复合物中释放出来，不能被 Fbw7 泛素化，这导致 c-Jun 的稳定性和积累增加。这些结果表明，Rack1 通过维持 JNK 或其他激酶磷酸化的 c-Jun 的稳定性，在肿瘤发生中起着非常重要的作用。
