TI - JNK -mediated BIM phosphorylation potentiates BAX -dependent apoptosis . AB - Trophic factor deprivation ( TFD ) activates c-Jun N-terminal kinases ( JNKs ) , culminating in coordinate AP1 -dependent transactivation of the BH3-only BCL-2 proteins BIM (EL) and HRK , which in turn are critical for BAX -dependent cytochrome c release , caspase activation , and apoptosis . Here , we report that TFD caused not only induction but also phosphorylation of BIM (EL) . Mitochondrially localized JNKs but not upstream activators , like mixed-lineage kinases ( MLKs ) or mitogen-activated protein kinase kinases ( MKKs ) , specifically phosphorylated BIM (EL) at Ser65 , potentiating its proapoptotic activity . Inhibition of the JNK pathway attenuated BIM (EL) expression , prevented BIM (EL) phosphorylation , and abrogated TFD -induced apoptosis . Conversely , activation of this pathway promoted BIM (EL) expression and phosphorylation , causing BIM - and BAX -dependent cell death . Thus , JNKs regulate the proapoptotic activity of BIM (EL) during TFD , both transcriptionally and posttranslationally .