Gas1

Gas1 (Growth Arrest Specific 1) is one of six structurally unrelated proteins that were identified by their increased expression in growth arrested cells relative to actively proliferating cells (1, 2). Following mitogenic stimulation, Gas1 expression is transcriptionally suppressed by c Myc as cells transit from G 0 to G1 phases of the cell cycle (3, 4). Overexpression of Gas1 prevents S phase entry and DNA synthesis (5). Gas1mediated blockade of the cell cycle is p53 dependent but does not require the transactivating domain of p53 (6). The human Gas1 cDNA encodes a 345 amino acid (aa) precursor that includes a 39 aa signal sequence, a 279 aa mature protein, and a 27 aa Cterminal propeptide. Gas1 contains Alarich and Asprich regions as well as an RGD sequence (5). Mature human and mouse Gas1 share 85% aa sequence identity. Human Gas1 is a 40 kDa GPIlinked glycoprotein that is uniformly distributed on the cell surface (7).

 In contact inhibited vascular endothelial cells, Gas1 is induced by VECadherin and VEGF expression and mediates the antiapoptotic effect of VEGF (8). In contrast, Gas1 is induced in hippocampal neurons after NMDA exposure but functions as a proapoptotic effector of NMDAmediated excitotoxicity (9). Gas1 exhibits a range of developmental actions including either promoting or inhibiting growth and differentiation of somite, limb, cerebellar, and eye tissues (10 14). Gas1 contributes to the antagonistic effect of Wnt proteins toward Shh function by binding the Nterminal region of Shh (11). The dependence of Gas1 function on the cellular context has been addressed by suggesting that Gas1 could function as a coreceptor for GDNF family ligands (15).