Functional interaction between retinoblastoma protein and stress-activatedprotein kinase in multiple myeloma cells

previous studies have demonstrated that gamma-irradiation (IR)-induced apop tosis in multiple myeloma (MM) is associated with activation of stress-acti vated protein kinase (SAPK), In the present study, we examined the molecule s downstream of SAPK/C-Jun N-terminal kinase (JNK), focusing on the role of retinoblastoma protein (Rb) during IR-induced MM cell apoptosis. The resul ts demonstrate that IR activates SAPK/JNK, which associates with Rb both in viva and in vitro. Far Western blot analysis confirms that SAPK/JNK binds directly to Rb. IR-activated SAPK/JNK phosphorylates Rb, and deletion of th e phosphorylation site in the COOH terminus domain of Rb abrogates phosphor ylation of Rb by SAPK/JNK. Taken together, our results suggest that Rb is a target protein of SAPK/JNK and that the association of SAPK/JNK and Rb med iates IR-induced apoptosis in MM cells.