Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) inresponse to DNA damage

Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic a gents is necessary for induction of apoptosis, We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mit ochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (T hr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant B cl-x(L) with the two threonines substituted by alanines (Ala-47, Ala-115) i s a more potent inhibitor of ionizing radiation-induced apoptosis, These fi ndings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genot oxic stress.