Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1835-1844 |
| Number of pages | 10 |
| Journal | Oncogene |
| Volume | 31 |
| Issue number | 14 |
| DOIs | |
| State | Published - Apr 5 2012 |
Bibliographical note
Funding Information:We thank Dr Wang Luhai and Dr Ronai Ze’ev for providing the HA-FL-Rack1, HA-WD1-4-Rack1 and HA-WD5-7-Rack1 vectors and Dr Wei Wenyi for providing the Flag-wtc-Jun, Flag-DJNK-c-Jun, Flag-AF-c-Jun and Flag-AF-DJNK-c-Jun plasmids. We also thank Dr Bohmann Dirk for providing the c-JunAlaand c-JunAspmutant c-Jun plasmids. This study was supported by The Hormel Foundation and National Institutes of Health grants CA077646, CA111536, CA120388, ES016548 and R37 CA081064.
Keywords
- Rack1
- c-Jun
- cell transformation
- degradation
- phosphorylation