Aproliferin--a human plasma protein that induces the irreversible loss of proliferative potential associated with terminal differentiation.

Cellular proliferation is regulated not only by the action of growth factors and growth inhibitors whose effects are reversible but also by factors that induce the irreversible loss of proliferative potential associated with the terminal event in cellular differentiation. The authors have employed 3T3 T mesenchymal stem cells as a model system to study the terminal event in cellular differentiation because in these cells' distinct nonterminal and terminal states of differentiation can be identified and because transition from the nonterminal to the terminal states of differentiation can be induced by human plasma. In this paper is reported the 20,000-fold purification of a component of human plasma that induces the terminal event in differentiation. This factor is shown to have an apparent molecular weight of approximately 45,000 and an isoelectric point of approximately 7.6. It is trypsin-sensitive, acid and heat-labile, and is resistant to treatment with dithiothreitol and alkali. The ability of this human plasma protein to induce the irreversible loss of proliferative potential associated with the terminal event in differentiation serves as the basis for its designation "aproliferin." The data in this paper in addition show that no other pharmacologic or physiologic agents have been identified that can mimic the biologic effect of aproliferin. Therefore, aproliferin appears to be a functionally distinct protein in human plasma.