Annexin A1 is regulated by domains cross-talk through post-translational phosphorylation and SUMOYlation
| Autor: | Robert Faure, Robert M. Tanguay, Halim Maaroufi, Danielle Caron, Sébastien Michaud |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
endocrine system SUMO protein Stimulation Protein Structure Secondary 03 medical and health sciences Mice 0302 clinical medicine EGF receptor Ubiquitin LNCaP Animals Humans Phosphorylation Nuclear export signal 030304 developmental biology Annexin A1 0303 health sciences Membranes biology Prostate Ubiquitination Sumoylation Cell Biology Molecular biology Cell biology Protein Structure Tertiary Secretory protein 030220 oncology & carcinogenesis biology.protein Mutagenesis Site-Directed Protein Processing Post-Translational |
| Zdroj: | Cellular Signalling. 25(10):1962-1969 |
| ISSN: | 0898-6568 |
| DOI: | 10.1016/j.cellsig.2013.05.028 |
| Popis: | Mouse prostate membrane-associated proteins of the annexin family showed changes in SUMOylation during androgen treatment. Among these the calcium-binding annexin A1 protein (ANXA1) was chosen for further characterization given its role in protein secretion and cancer. SUMOylation of ANXA1 was confirmed by overexpressing SUMO-1 in LNCaP cells. Site-directed mutagenesis indicated that K257 located in a SUMOylation consensus motif in the C-terminal calcium-binding DA3 repeat domain is SUMOylated. Mutation of the N-terminal Y21 decreased markedly the SUMOylation signal while EGF stimulation increased ANXA1 SUMOylation. A structural analysis of ANXA1 revealed that K257 is located in a hot spot where Ca2 + and SUMO-1 bind and where a nuclear export signal and a polyubiquitination site are also present. Also, Y21 is buried inside an α-helix structure in the Ca2 +-free conformation implying that Ca2 + binding, and the subsequent expelling of the N-terminal α-helix in a disordered conformation, is permissive for its phosphorylation. These results show for the first time that SUMOylation can be regulated by an external signal (EGF) and indicate the presence of a cross-talk between the N-terminal and C-terminal domains of ANXA1 through post-translational modifications. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect