Gadd45b mediates Fas-induced apoptosis by enhancing the interaction between p38 and retinoblastoma tumor suppressor.
Gadd45b has been known as a positive mediator of apoptosis induced by certain cytokines and oncogenes. Here, we identified Gadd45b as an effector of Fas-induced apoptosis and found that p38-mediated Rb hyperphosphorylation is one of the mechanisms of Fas-induced apoptosis in murine hepatocyte AML12 cells. Gadd45b has been shown to activate p38 through its physical interaction with MTK1 and induce apoptosis. However, in this study, we have showed that the function of Gadd45b during Fas-induced apoptosis in AML12 cells is different from that reported in previous studies. Depletion of Gadd45b expression did not inhibit the phosphorylation of p38, but it suppressed p38-mediated Rb phosphorylation and apoptosis in response to Fas stimulation by reducing the interaction between p38 and Rb. Ectopic expression of Gadd45b was sufficient to enhance this interaction. These findings suggest that Gadd45b mediates p38-induced Rb phosphorylation by enhancing the interaction between p38 and Rb during Fas-induced apoptosis in murine hepatocytes.
Cho
Hee Jun
HJ
Department of Microbiology/Research Institute of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Korea.
Park
Sun-Mi
SM
Hwang
Eun Mi
EM
Baek
Kyoung Eun
KE
Kim
In-Kyu
IK
Nam
In-Koo
IK
Im
Min-Ju
MJ
Park
Seung-Ho
SH
Bae
Seran
S
Park
Jae-Yong
JY
Yoo
Jiyun
J
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D051379:Mice; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D016160:Retinoblastoma Protein; D019014:fas Receptor; D048051:p38 Mitogen-Activated Protein Kinases; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C093642:SB 203580