A M Zubiaga

E2F-1 Functions in Mice to Promote Apoptosis and Suppress Proliferation

Members of the E2F transcription factor family (E2F-1-E2F-5) are believed to be critical positive regulators of cell cycle progression in eukaryotes although the in vivo functions of the individual E2Fs have not been elucidated. Mice were generated that lack E2F-1 and, surprisingly, these mice develop and reproduce normally. However, E2F-1-/- mice exhibit a defect in T lymphocyte development leading to an excess of mature T cells due to a maturation stage-specific defect in thymocyte apoptosis. As E2F-1-/- mice age they exhibit a second phenotype marked by aberrant cell proliferation. These findings suggest that while certain members of the E2F family may positively regulate cell cycle progression, E2F-1 functions to regulate apoptosis and to suppress cell proliferation.

Tyrosine protein phosphorylation is required for protein kinase C-mediated proliferation in T cells

We have studied the role of tyrosine kinase in PMA‐stimulated T cells. Protein kinase C (PKC)‐mediated D10A cell proliferation is inhibited by the specific inhibitor of tyrosine kinase, tyrphostin. This inhibitor selectively blocks the mRNA expression of the proto‐oncogene e‐mye in response to the phorbol ester. On the other hand, the same doses of this inhibitor do not affect the mRNA expression of the proto‐oncogene c‐for in PMA‐stimulated D10A cells. Phorbol esters induce in this T cell line the tyrosine phosphorylation of a unique protein of 42 kDa and the enzyme PKC is required for this activity.