PMID:20516211

Citation	Da Costa, CR, Villadiego, J, Sancho, R, Fontana, X, Packham, G, Nateri, AS and Behrens, A (2010) Bag1-L is a phosphorylation-dependent coactivator of c-Jun during neuronal apoptosis. Mol. Cell. Biol. 30:3842-52
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.
Links	PubMed PMC2916400 Online version:10.1128/MCB.01610-09
Keywords	Animals; Apoptosis/genetics; Apoptosis/physiology; Cell Death/genetics; DNA-Binding Proteins; MAP Kinase Signaling System/genetics; Nerve Degeneration/genetics; Nerve Degeneration/metabolism; Nerve Degeneration/pathology; Neurons/metabolism; Neurons/pathology; Neurons/physiology; PC12 Cells; Phosphorylation; Rats; Transcription Factor AP-1/genetics; Transcription Factor AP-1/metabolism; Transcription Factors
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