Retinoblastoma and p53 gene products may have an active role in mediating growth-suppressing effect of GAS1 (Del Sal et al.,1992). GAS1 and p53 expression found during the early stages of development of placenta, heart and kidney during embryogenesis in rat (Rees et al.,1999). Overexpression of MDM2 or p53 mutation inhibits GAS1-mediated growth-suppressing pathway (Evdokiou et al.,1998).
NCBI Summary:
Growth arrest-specific 1 plays a role in growth suppression. GAS1 blocks entry to S phase and prevents cycling of normal and transformed cells. Gas1 is a putative tumor suppressor gene. [provided by RefSeq, Jul 2008]
General function
Cell death/survival, Apoptosis, Tumor suppressor
Comment
GAS1 is a growth-arrest gene that inhibits DNA synthesis through expression of the GAS1 protein, an integral plasma membrane protein (Del Sal et al.,1992). The location of GAS1 at a site of deletion in myeloid malignancies, together with the demonstration that GAS1 suppresses DNA synthesis, suggests it is a tumor suppressor gene. Human GAS1 may be a target for genetic alterations leading to its inactivation in tumor cells (Del Sal et al.,1994).
Cellular localization
Comment
Ovarian function
Ovulation, Luteinization, Luteolysis, Early embryo development
Comment
Growth arrest specific 1 (Gas1) and glial cell line-derived neurotrophic factor receptor α1 (Gfrα1), two mouse oocyte glycosylphosphatidylinositol-anchored proteins, are involved in fertilisation. Agopiantz M et al. (2017) Recently, Juno, the oocyte receptor for Izumo1, a male immunoglobulin, was discovered. Juno is an essential glycosylphosphatidylinositol (GIP)-anchored protein. This result did not exclude the participation of other GIP-anchored proteins in this process. After bibliographic and database searches we selected five GIP-anchored proteins (Cpm, Ephrin-A4, Gas1, Gfra1 and Rgmb) as potential oocyte candidates participating in fertilisation. Western blot and immunofluorescence analyses showed that only three were present on the mouse ovulated oocyte membrane and, of these, only two were clearly involved in the fertilisation process, namely growth arrest specific 1 (Gas1) and glial cell line-derived neurotrophic factor receptor α1 (Gfrα1). This was demonstrated by evaluating oocyte fertilisability after treatment of oocytes with antibodies against the selected proteins, with their respective short interference RNA or both. Gfrα1 and Gas1 seem to be neither redundant nor synergistic. In conclusion, oocyte Gas1 and Gfrα1 are both clearly involved in fertilisation.//////////////////
Growth Arrest Specific-1 (GAS1) Is a C/EBP Target Gene That Functions in Ovulation and Corpus Luteum Formation in Mice. Ren YA et al. (2016) Ovulation and luteinization are initiated in preovulatory follicles by the luteinizing hormone (LH) surge; however the signaling events that mediate LH actions in these follicles remain incompletely defined. Two key transcription factors that are targets of LH surge are C/EBPalpha and C/EBPbeta and their depletion in granulosa cells results in complete infertility. Microarray analyses of these mutant mice revealed altered expression of a number of genes including growth arrest specific-1 (Gas1). To investigate functions of Gas1 in ovulation- and luteinization-related processes, we crossed Cyp19a1-Cre and Gas1(flox/flox) mice to conditionally delete Gas1 in granulosa and cumulus cells. While expression of Gas1 is dramatically increased in granulosa and cumulus cells around 12-16 h post-human chorionic gonadotropin (hCG) stimulation in wild type mice, this increase is abolished in Cebpa/b double mutant and in Gas1 mutant mice. GAS1 is also dynamically expressed in stromal cells of the ovary independent of C/EBPalpha/beta. Female Gas1 mutant mice are fertile, exhibit enhanced rates of ovulation, increased fertility, and higher levels of Areg and Lhcgr mRNA in granulosa cells. The morphological appearance and vascularization of corpora lutea appeared normal in these mutant females. Interestingly, levels of mRNA for a number of genes (Cyp11a1, Star, Wnt4, Prlr, Cd52, and Sema3a) associated with luteinization are decreased in corpora lutea of Gas1 mutant mice as compared with controls at 24 h post-hCG; these differences were no longer detectable by 48 h post-hCG. The C/EBP target Gas1 is induced in granulosa cells and is associated with ovulation and luteinization.//////////////////
Expression regulated by
LH
Comment
Ovarian localization
Luteal cells, Stromal cells
Comment
Follicle stages
Corpus luteum
Comment
GAS1 showed sharp up-regulation during physiological apoptosis in rat ovarian corpus luteum (Guo et al.,1998).
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: type: null mutation fertility: fertile Comment: Growth Arrest Specific-1 (GAS1) Is a C/EBP Target Gene That Functions in Ovulation and Corpus Luteum Formation in Mice. Ren YA et al. (2016) Ovulation and luteinization are initiated in preovulatory follicles by the luteinizing hormone (LH) surge; however the signaling events that mediate LH actions in these follicles remain incompletely defined. Two key transcription factors that are targets of LH surge are C/EBPalpha and C/EBPbeta and their depletion in granulosa cells results in complete infertility. Microarray analyses of these mutant mice revealed altered expression of a number of genes including growth arrest specific-1 (Gas1). To investigate functions of Gas1 in ovulation- and luteinization-related processes, we crossed Cyp19a1-Cre and Gas1(flox/flox) mice to conditionally delete Gas1 in granulosa and cumulus cells. While expression of Gas1 is dramatically increased in granulosa and cumulus cells around 12-16 h post-human chorionic gonadotropin (hCG) stimulation in wild type mice, this increase is abolished in Cebpa/b double mutant and in Gas1 mutant mice. GAS1 is also dynamically expressed in stromal cells of the ovary independent of C/EBPalpha/beta. Female Gas1 mutant mice are fertile, exhibit enhanced rates of ovulation, increased fertility, and higher levels of Areg and Lhcgr mRNA in granulosa cells. The morphological appearance and vascularization of corpora lutea appeared normal in these mutant females. Interestingly, levels of mRNA for a number of genes (Cyp11a1, Star, Wnt4, Prlr, Cd52, and Sema3a) associated with luteinization are decreased in corpora lutea of Gas1 mutant mice as compared with controls at 24 h post-hCG; these differences were no longer detectable by 48 h post-hCG. The C/EBP target Gas1 is induced in granulosa cells and is associated with ovulation and luteinization.//////////////////