Disappearance of statin, a protein marker for non-proliferating and senescent cells, following serum-stimulated cell cycle entry.

Statin, a protein of 57,000 D, is present in the nuclei of quiescent or senescent fibroblasts (Wang, E, J cell biol 100 (1985) 545), but is absent in their young replicating counterparts. Immunohistochemical survey of a variety of tissues demonstrates that the presence of statin is a marker for cells that are no longer involved in proliferation, i.e. those cells that are terminally differentiated. Statin expression was examined by immunofluorescence microscopy in serum-starved cultures whose replication had been reinitiated by raising the serum concentration from 0.5 to 10%. Prior to serum addition, more than 85% of the cells stained positively for statin. After stimulation with serum, the expression of statin disappeared rapidly within the first 12-14 h. On the other hand, an increase in the level of DNA synthesis, signifying entry into S phase, was observed initially at 18 h after serum stimulation, and reached maximal levels 6 h later. Immunoprecipitation of statin derived from cells harvested at different intervals after serum stimulation revealed that the level of statin synthesis was reduced by 4 h and was hardly detectable at 8 h. These results demonstrate that the synthesis of statin occurs primarily when cells are in a quiescent state, and declines rapidly when cells are induced to proliferate; this decline precedes the transition from G1 to S phase.