title: Functional interaction between retinoblastoma protein and stress-activated protein kinase in multiple myeloma cells.
abstract: Previous studies have demonstrated that gamma-irradiation (IR)-induced apoptosis in multiple myeloma (MM) is associated with activation of stress-activated protein kinase (SAPK). In the present study, we examined the molecules downstream of SAPK/C-Jun N-terminal kinase (JNK), focusing on the role of retinoblastoma protein (Rb) during IR-induced MM cell apoptosis. The results demonstrate that IR activates SAPK/JNK, which associates with Rb both in vivo and in vitro. Far Western blot analysis confirms that SAPK/JNK binds directly to Rb. IR-activated SAPK/JNK phosphorylates Rb, and deletion of the phosphorylation site in the COOH terminus domain of Rb abrogates phosphorylation 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 mediates IR-induced apoptosis in MM cells.
authors: Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: D
authors: D
authors: Chauhan
authors: T
authors: T
authors: Hideshima
authors: S
authors: S
authors: Treon
authors: G
authors: G
authors: Teoh
authors: N
authors: N
authors: Raje
authors: S
authors: S
authors: Yoshihimito
authors: Y T
authors: YT
authors: Tai
authors: W
authors: W
authors: Li
authors: J
authors: J
authors: Fan
authors: J
authors: J
authors: DeCaprio
authors: K C
authors: KC
authors: Anderson
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009101:Multiple Myeloma / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation / Q000528:radiation effects; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D016160:Retinoblastoma Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases