| First Author | Da Costa CR | Year | 2010 |
| Journal | Mol Cell Biol | Volume | 30 |
| Issue | 15 | Pages | 3842-52 |
| PubMed ID | 20516211 | Mgi Jnum | J:162788 |
| Mgi Id | MGI:4819895 | Doi | 10.1128/MCB.01610-09 |
| Citation | Da Costa CR, et al. (2010) Bag1-L is a phosphorylation-dependent coactivator of c-Jun during neuronal apoptosis. Mol Cell Biol 30(15):3842-52 |
| abstractText | 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. |
