EXPRESSION OF THE SIL GENE IS CORRELATED WITH GROWTH INDUCTION AND CELLULAR PROLIFERATION

The SIL gene was discovered at the site of a cancer-associated interst itial deletion in which its promoter assumed the regulation of a secon d gene, SCL. The human SIL gene encodes a 1287-amino acid cytosolic pr otein that has been found to be highly conserved in the mouse. SIL is expressed in proliferating cells and is down-regulated when cellular p roliferation ceases because of serum starvation, contact inhibition, o r induction of terminal differentiation. SIL is induced within 1 h of stimulation by 20% serum in growth-arrested 3T3 cells. This induction is independent of protein synthesis because ''superinduction'' is obse rved in the presence of the protein synthesis inhibitor cyclohexamide. Thus, SIL is an immediate-early gene. Upon release from serum starvat ion of 3T3 fibroblasts SIL mRNA and protein levels display a biphasic pattern during the first cell cycle. In contrast, in exponentially gro wing EL4 lymphoblasts, SIL mRNA is stable throughout the cell cycle, w hereas SIL protein accumulates into G(2) phase and then falls precipit ously at the completion of the cell cycle. This pattern of cell cycle expression suggests that SIL may play an important role in cellular gr owth and proliferation.