title: Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation.
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.
authors.affiliation: Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, 55912, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: F
authors.initials: F
authors.lastname: Zhu
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: C
authors.initials: C
authors.lastname: Peng
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Cho
authors.forename: K
authors.initials: K
authors.lastname: Yao
authors.forename: T A
authors.initials: TA
authors.lastname: Zykova
authors.forename: A M
authors.initials: AM
authors.lastname: Bode
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D044783:F-Box Proteins / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D019204:GTP-Binding Proteins / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology*; D010766:Phosphorylation; D055550:Protein Stability; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D009363:Neoplasm Proteins; D016755:Proto-Oncogene Proteins c-jun; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D044767:Ubiquitin-Protein Ligases; D019204:GTP-Binding Proteins