Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with modulation by Smad.
Bone morphogenetic proteins, including growth/differentiation factor-5 (GDF-5), are multifunctional cytokines. Recent studies of intracellular signal transduction mechanisms for the transforming growth factor-beta superfamily have focused on Smad proteins. However, scant attention has been given to the mechanism by which GDF-5 exerts its negative growth effect on immunological competent cells. In the present study, we demonstrated that GDF-5 induced cell cycle arrest in the G1 phase before the appearance of apoptosis in mouse B cell hybridoma HS-72 cells, while the ectopic expression of Smad6 and Smad7 in HS-72 cells suppressed the GDF-5-induced G1 cell cycle arrest by abolishing the expression of p21(CIP-1/WAF-1) and hypophosphorylation of retinoblastoma protein. Moreover, we found that Smad6 and Smad7 suppressed GDF-5-induced apoptosis in HS-72 cells. These findings indicated that Smad6 and Smad7 exhibit inhibitory effects toward GDF-5-mediated signaling in B lineage cells.
Nakahara
Takahiro
T
First Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 803-8580, Kitakyushu, Japan.
Tominaga
Kazuhiro
K
Koseki
Takeyoshi
T
Yamamoto
Matsuo
M
Yamato
Kenji
K
Fukuda
Jinichi
J
Nishihara
Tatsuji
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002460:Cell Line; D019070:Cell Lineage; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects; D055428:Growth Differentiation Factor 5; D006825:Hybridomas; D051379:Mice; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D016160:Retinoblastoma Protein; D051905:Smad6 Protein; C497803:Smad6 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D015534:Trans-Activators