Activins, members of the transforming growth factor-β family, have been implicated in the regulation of growth and differentiation of various types of cells. We have recently found that activin A induces apoptotic cell death of plasmacytic cells including B cell hybridoma cells and myeloma cells. In the present study, we demonstrated that activin A caused cell-cycle arrest in the G1 phase before apPearance of apoptotic cells in mouse B cell hybridoma cells. Phosphorylation of retinoblastoma protein (Rb) and in vitro Rb kinase activity of cyclin-dependent kinase (CDK)4 was inhibited in activin A- treated cells. Analysis of expression of genes regulating Rb phosphorylation revealed that activin A suppressed cyclin D2, the sole D-tyPe cyclin gene expressed in the hybridoma cells, and activated p21(CIP1/WAF1) but had no effect on expression of cyclin-dependent kinases (CDK2, CDK4, CDK6) and other CDK inhibitors (p27(KIP1), p16(INK4a), p15(INK4b)). Modulation of cyclin D2 and p21(CIP1/WAF1) expression resulted in a decrease in level of cyclin D2- CDK4 complex and an increase in level of CDK4 complexed with p21(CIP1/WAF1). Moreover, overexpression of cyclin D2 partially abrogated inhibition of Rb phosphorylation and G1 arrest in the hybridoma cells.
ASJC Scopus subject areas
- Molecular Biology