Bag1-L is a phosphorylation-dependent coactivator of c-Jun during neuronal apoptosis

Da Costa, Clive R.; Villadiego, Javier; Sancho, Rocio; Fontana, Xavier; Packham, Graham; Nateri, Abdolrahman S.; Behrens, Axel

Abstract

In the nervous system, cell death by apoptosis plays a critical role during normal development and pathological neurodegeneration. Jun N-terminal kinases (JNKs) are essential regulators of neuronal apoptosis. The AP-1 transcription factor c-Jun is phosphorylated at multiple sites within its transactivation domain by the JNKs, and c-Jun phosphorylation is required for JNK-induced neurotoxicity. While the importance of c-Jun as a mediator of apoptotic JNK signaling in neurons is firmly established, the molecular mechanism underlying the requirement for c-Jun N-terminal phosphorylation is enigmatic. Here we identify the multifunctional protein Bag1-L as a coactivator of phosphorylated c-Jun. Bag1-L preferentially interacts with N-terminally phosphorylated c-Jun, and Bag1-L greatly augments transcriptional activation by phosphorylated c-Jun. Chromatin immunoprecipitation experiments revealed binding of Bag1-L to the promoters of proapoptotic AP-1 target genes, and overexpression of Bag1-L augmented cell death in primary neurons. Therefore, Bag1-L functions as a coactivator regulating neurotoxicity mediated by phosphorylated c-Jun. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Citation

Da Costa, C. R., Villadiego, J., Sancho, R., Fontana, X., Packham, G., Nateri, A. S., & Behrens, A. (2010). Bag1-L is a phosphorylation-dependent coactivator of c-Jun during neuronal apoptosis. Molecular and Cellular Biology, 30(15), 3842-3852. https://doi.org/10.1128/MCB.01610-09

• Journal Article Type: Article
• Online Publication Date: Mar 30, 2023
• Publication Date: Aug 1, 2010
• Deposit Date: Sep 11, 2024
• Journal: Molecular and Cellular Biology
• Print ISSN: 0270-7306
• Electronic ISSN: 1098-5549
• Publisher: American Society for Microbiology
• Peer Reviewed: Peer Reviewed
• Volume: 30
• Issue: 15
• Pages: 3842-3852
• DOI: https://doi.org/10.1128/MCB.01610-09
• Public URL: https://nottingham-repository.worktribe.com/output/39458028
• Publisher URL: https://www.tandfonline.com/doi/full/10.1128/MCB.01610-09
• Related Public URLs: https://pubmed.ncbi.nlm.nih.gov/20516211/