Open AccessBag1-L Is a Phosphorylation-Dependent Coactivator of c-Jun during Neuronal Apoptosis
Author(s) -
Clive Da Costa,
Javier Villadiego,
Rocı́o Sancho,
Xavier Fontana,
Graham Packham,
Abdolrahman S. Nateri,
Axel Behrens
Publication year - 2010
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01610-09
Subject(s) - biology , phosphorylation , transactivation , coactivator , c jun , microbiology and biotechnology , neurotoxicity , neurodegeneration , programmed cell death , kinase , chromatin immunoprecipitation , transcription factor , apoptosis , signal transduction , promoter , biochemistry , gene expression , gene , chemistry , medicine , organic chemistry , toxicity , disease
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.