The role of Gas1 in embryonic development and its implications for human disease.
Growth Arrest Specific Gene 1 (Gas1) has long been regarded as a cell cycle inhibitor of the G(0) to S phase transition. How GAS1, a GPI-anchored plasma membrane protein, directs intracellular changes without an extracellular ligand or a transmembrane protein partner has been puzzling. A recent series of biochemical and molecular genetic studies assigned the mammalian Hedgehog (HH) growth factor to be a ligand for GAS1 in vitro and in vivo. HH has enjoyed considerable attention for its profound role in embryonic patterning as a classic morphogen, i.e. inducing various cell types in a concentration-dependent manner. GAS1 appears to help transform the HH concentration gradient into its morphogenic activity gradient by acting cooperatively with the HH receptor, the 12-transmembrane protein Patched 1 (PTC1). These findings provoke intriguing thoughts on how HH and GAS1 may coordinate cell proliferation and differentiation to create biological patterns. The role of HH extends to human genetic diseases, stem cell renewal, and cancer growth, and we consider the possibility of GAS1's involvement in these processes as well.
Martinelli
David C
DC
Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland 21218, USA. david@jhu.edu
Fan
Chen-Ming
CM
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D004198:Disease Susceptibility / Q000196:embryology* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D058851:GPI-Linked Proteins; D053823:Hedgehog Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D009369:Neoplasms / Q000196:embryology* / Q000209:etiology / Q000378:metabolism*
D018797:Cell Cycle Proteins; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; D053823:Hedgehog Proteins; D008024:Ligands; D008565:Membrane Proteins