Spa-1 genes is one of the secondary response genes specifically induced to express in the lymphoid cells following the mitogenic stimulations by antigens or mitogenic cytokines. Gene transfection experiments indicate that Spa-1 protein exhibits negative effect on cell growth and induces cell death when ectopically overexpressed. Spa-1 protein is a nuclear protein and suggested to function through the interaction with Ran, so far the only small G protein present in the nuclei, While Spa-1 mRNA is expressed in normal proliferating lymphocytes as well as factor-dependent cell lines, little mRNA is expressed in autonomously growing leukemic lines, suggesting the active repression of Spa-1 transcription in transformed cells. Analysis of this mechanism may provide a new insight into the transformation processes in lymphoid cells.