Cells arrested in G1 by the v-Abl tyrosine kinase do not express cyclin A despite the hyperphosphorylation of RB

Abstract

The v-Abl tyrosine kinase encoded by the Abelson murine leukemia virus (A-MuLV) can either stimulate or inhibit cell proliferation, depending on the cell context. In a NIH-3T3-derived cell line, N3T3, v-Abl blocks the serum- induced entry into S phase. In these G1-arrested cells v-Abl does not interfere with the activation of cyclin D1 or cyclin E-dependent kinases. As a result, v-Abl does not block the hyperphosphorylation and inactivation of the retinoblastoma protein RB. However, activation of cyclin A. dependent kinase is inhibited due to a v-Abl-induced block in the accumulation of cyclin A mRNA and protein. Ectopic expression of cyclin A enabled the v. Abl-arrested cells to enter S phase, whereas cyclins E and D1, or E2Fs 1 and 4 could not overcome the v-Abl arrest. Taken together, these results suggest that v-Abl tyrosine kinase arrests cell cycle progression in G1 by inhibiting the expression of cyclin A.