Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation.
Oncogene
; 31(14): 1835-44, 2012 Apr 05.
Article
in En
| MEDLINE
| ID: mdl-21860413
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins c-jun
/
Receptors, Cell Surface
/
Cell Cycle Proteins
/
GTP-Binding Proteins
/
Ubiquitin-Protein Ligases
/
F-Box Proteins
/
Neoplasm Proteins
Limits:
Animals
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2012
Document type:
Article
Affiliation country: