Cells arrested in G1 by the v-Abl tyrosine kinase do not express cyclin A despite the hyperphosphorylation of RB.
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.
Chen
Y
Y
Department of Biology and Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0347, USA.
Knudsen
E S
ES
Wang
J Y
JY
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle; D016213:Cyclins / Q000378:metabolism*; D051379:Mice; D016374:Oncogene Proteins v-abl / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*
D016213:Cyclins; D016374:Oncogene Proteins v-abl; D016160:Retinoblastoma Protein; D011505:Protein-Tyrosine Kinases