Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3
AUTOR(ES)
Qiu, Xiao-Bo
FONTE
National Academy of Sciences
RESUMO
The epidermal growth factor receptor (EGFR/ErbB) family of receptor tyrosine kinases plays fundamental roles in the regulation of cell survival, proliferation, and differentiation. Here, we present evidence that ErbB3 is degraded by proteasomes, and that Nrdp1 (referred to as FLRF in mice) associates with ErbB3 and stimulates its ubiquitination and degradation by proteasomes. Nrdp1 mRNAs are expressed in a variety of human tissues. The N-terminal half of Nrdp1 possesses an atypical RING finger domain, which is required for enhancing ErbB3 degradation. Its C-terminal half by itself associates with ErbB3 and raises ErbB3 levels in cells, probably by acting as a dominant–negative form of Nrdp1. In cell-free systems, Nrdp1 has ubiquitin ligase (E3) activity and ubiquitinates ErbB3, as well as itself, in the presence of the ubiquitin-carrier protein (E2), UbcH5. These data indicate that Nrdp1 is a RING finger-type of ubiquitin ligase, which promotes degradation of ErbB3 by proteasomes and, thus, may be an important factor influencing cell growth.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=137506Documentos Relacionados
- ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor.
- Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family.
- Neuregulin receptors, erbB3 and erbB4, are localized at neuromuscular synapses.
- The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation
- The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system