The soluble glucocorticoid-induced tumor necrosis factor receptor causes cell cycle arrest and apoptosis in murine macrophages.
In order to clarify the mechanism by which soluble GITR (sGITR) inhibits the survival of murine macrophages we examined its effect on the macrophage cell cycle. Soluble GITR induced G1 phase arrest followed by apoptosis. It also reduced the expression of cyclins D2 and A, and of cdk4, resulting in reduced cdk2 and cdk4 activities. These findings suggest that sGITR arrests division of the macrophages in G1 by lowering the activities of cdk2 and cdk4, and that this leads to apoptosis.
Shin
Hyun-Hee
HH
Department of Biological Sciences and the Immunomodulation Research Center, University of Ulsan, Ulsan 680-749, Republic of Korea.
Kim
Soo-Jin
SJ
Lee
Hee-Sook
HS
Choi
Hye-Seon
HS
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D016193:G1 Phase; D053450:Glucocorticoid-Induced TNFR-Related Protein; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology; D017434:Protein Structure, Tertiary; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D016213:Cyclins; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C106544:Tnfrsf18 protein, mouse; D009569:Nitric Oxide; D018844:Cyclin-Dependent Kinases