Cell cycle regulation of a lympho-hematopoietic specific Rap1GTPase-activating protein, Spa-1 in lymphocyres.

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We have cloned a human homologue of mouse Spa-1 gene (SPA-1) which encodes a 130 kDa (p130) cytoplasmic protein with SH3-binding, Rap1GAP.PEST and leucine zipper/coiled coil domains. p130 expressed in a Baculovirus system exhibits a specfic GTPase-activating activity against Rap1. Overexpression of a truncated Spa-1cDNA in NIH3T3 cells apparently disturbed the entry into the cell cycle in the G0-arrested NIH3T3 cells following mitogenic stimulation, suggesting that the protein is critically involved in the cell cycle regulation via the interaction with Rap1. Genomic mapping indicated that Spa-1 is located at the most centromeric region of chromosome 19 in mouse and at the centrimieric neighborhood of CCND1/PRAD1, a presumed BCL1 oncogene, at 11q13.3 in human.