Smad7 Is an Activin-inducible Inhibitor of Activin-induced Growth Arrest and Apoptosis in Mouse B Cells

• Published in: The Journal of biological chemistry 1998-09, Vol.273 (38), p.24293-24296
• Main Authors: Ishisaki, Akira, Yamato, Kenji, Nakao, Atsuhito, Nonaka, Koji, Ohguchi, Masahiro, ten Dijke, Peter, Nishihara, Tatsuji
• Format: Article
• Language: English
• Subjects: Activins; Animals; Apoptosis - drug effects; Apoptosis - physiology; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - physiology; Cell Cycle - drug effects; Cell Cycle - physiology; Cell Division - drug effects; Cell Line; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; G1 Phase; Growth Substances - pharmacology; Hybridomas; Inhibins - pharmacology; Kinetics; Mice; Recombinant Proteins - biosynthesis; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Signal Transduction; Smad7 Protein; Trans-Activators - biosynthesis; Trans-Activators - genetics; Trans-Activators - physiology; Transcription, Genetic - drug effects; Transfection; Transforming Growth Factor beta - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.38.24293

Members of the transforming growth factor-β (TGF-β) family, which includes the activins, relay signals from serine/threonine kinase receptors in membrane to nucleus via intracellular Sma- and Mad-related (Smad) proteins. Inhibitory Smad proteins were found to prevent the interaction between the serine/threonine kinase receptors and pathway-restricted Smad proteins. Smad7 was identified as a TGF-β-inducible antagonist of TGF-β signaling, and it may participate in a negative feedback loop to control TGF-β signaling. Here we demonstrate that the mRNA expression of Smad7 is induced by activin A in mouse B cell hybridoma HS-72 cells, which undergo growth arrest and apoptosis upon exposure to activin A. The ectopic expression of mouse Smad7 in HS-72 cells suppressed the activin A-induced cell cycle arrest in the G1 phase by abolishing the activin A-induced expression of p21CIP1/WAF1 and hypophosphorylation of retinoblastoma protein. Furthermore, Smad7 expression suppressed activin A-induced apoptosis in HS-72 cells. Thus, our data indicate that Smad7 is an activin A-inducible antagonist of activin A-induced growth arrest and apoptosis of B lineage cells.