Disclosed herein are compositions and methods for increasing protein
production from a cell culture. By switching the cells from a replicative
to a productive state (RP switch), protein biosynthesis is extended. The
productive state is a pseudo-senescent state. This pseudo-senescent state
can be induced by transforming the cells with a vector expressing a cell
cycle inhibitor. Expression of the cell cycle inhibitor within the cell,
because it does not cause cell death, allows for cells to be maintained
in culture for longer periods. The invention allows for controlled
enhanced protein biosynthetic productivity of cell lines for commercial
and research purposes.