Alternative titles; symbols
HGNC Approved Gene Symbol:ARHGAP35
Cytogenetic location:19q13.32 Genomic coordinates(GRCh38) :19:46,860,997-47,005,077 (from NCBI)
The glucocorticoid receptor (GCCR;138040) is a member of the superfamily of nuclear receptors, which function as ligand-dependent, transacting regulatory proteins. Glucocorticoid receptor DNA-binding factor-1 (GRLF1) is thought to repress transcription of GCCR in response to glucocorticoids, thus damping the response of the liver to glucocorticoid stimulation (LeClerc et al., 1991).
Using polyclonal antibodies against purified GRLF1,LeClerc et al. (1991) isolated a partial GRLF1 cDNA encoding a deduced 835-amino acid protein. The protein contains 3 possible zinc finger structures and a leucine zipper motif that contains 1 cysteine. Western blot analysis detected expression of a 94-kD GRLF1 protein.
By sequence comparisons with rat p190A, database searching, and RT-PCR analysis,Tikoo et al. (2000) obtained a full-length cDNA sequence encoding GRLF1, the human homolog of p190A. The deduced 1,514-amino acid protein is 97% identical to the rat sequence. The first 1,287 residues, including the GTPase and middle domains, are encoded by the 3.7-kb exon 1, similar to the structure observed in p190B (ARHGAP5;602680).
By Southwestern blot analysis and use of band shift assays with transfected COS-1 extracts,LeClerc et al. (1991) demonstrated that GRLF1 interacts with the GCCR promoter. They also showed that GRLF1 functions as a hormone-independent repressor of GCCR expression. They hypothesized that GRLF1 represses GCCR expression through direct interaction with a unique sequence in the GCCR regulatory region. Similar sequence motifs are found in the regulatory regions of the insulin receptor, androgen receptor, and c-myc genes.
In rats,LeClerc et al. (1991) observed a decrease in GRFL1 mRNA after adrenalectomy and a slight increase in the level of mRNA after subsequent glucocorticoid dexamethasone hormone treatment. The authors concluded that GRLF1 mRNA levels are regulated by glucocorticoids.
Wildenberg et al. (2006) found that depletion of delta-catenin (CTNND1;601045) in NIH3T3 mouse fibroblasts by small interfering RNA caused constitutive activation of Rho, cell transformation, loss of contact inhibition, and growth in the absence of serum. Moreover, Pdgf receptor (see173490) and integrin signaling pathways involved in remodeling the actin cytoskeleton were selectively impaired.Wildenberg et al. (2006) traced these effects to obligatory roles of delta-catenin and p190RhoGAP (Arhgap35) in a pathway that connects Rac activation to Rho inhibition. They concluded that delta-catenin and ARHGAP35 use Rho GTPases to mediate crosstalk between a wide variety of receptors to coordinate cadherin function with other activities that direct cell adhesion, motility, and proliferation.
Mammoto et al. (2009) showed that the Rho inhibitor p190RhoGAP (GRLF1) controls capillary network formation in vitro in human microvascular endothelial cells and retinal angiogenesis in vivo by modulating the balance of activities between 2 antagonistic transcription factors, TFII-I (GTF2I;601679) and GATA2 (137295), that govern gene expression of the VEGF receptor VEGFR2 (191306). Moreover, this angiogenesis signaling pathway is sensitive to extracellular matrix elasticity as well as soluble VEGF.Mammoto et al. (2009) suggested that this finding represented the first known functional crossantagonism between transcription factors that controls tissue morphogenesis, and that responds to both mechanical and chemical cues.
By Southern blot analysis,Tikoo et al. (2000) determined that GRLF1 is a single-copy gene on chromosome 19. Using FISH and radiation hybrid analysis, they localized the GRLF1 gene to 19q13.2-q13.4, a region known to be altered in gliomas and pancreatic, ovarian, and thyroid tumors.
LeClerc, S., Palaniswami, R., Xie, B., Govdan, M. V.Molecular cloning and characterization of a factor that binds the human glucocorticoid receptor gene and represses its expression. J. Biol. Chem. 266: 17333-17340, 1991. [PubMed:1894621,related citations]
Mammoto, A., Connor, K. M., Mammoto, T., Yung, C. W., Huh, D., Aderman, C. M., Mostoslavsky, G., Smith, L. E. H., Ingber, D. E.A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457: 1103-1108, 2009. [PubMed:19242469,images,related citations] [Full Text]
Tikoo, A., Czekay, S., Viars, C., White, S., Heath, J. K., Arden, K., Maruta, H.p190-A, a human tumor suppressor gene, maps to the chromosomal region 19q13.3 that is reportedly deleted in some gliomas. Gene 257: 23-31, 2000. [PubMed:11054565,related citations] [Full Text]
Wildenberg, G. A., Dohn, M. R., Carnahan, R. H., Davis, M. A., Lobdell, N. A., Settleman, J., Reynolds, A. B.p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. Cell 127: 1027-1039, 2006. [PubMed:17129786,related citations] [Full Text]
Alternative titles; symbols
HGNC Approved Gene Symbol: ARHGAP35
Cytogenetic location: 19q13.32 Genomic coordinates(GRCh38) : 19:46,860,997-47,005,077(from NCBI)
The glucocorticoid receptor (GCCR; 138040) is a member of the superfamily of nuclear receptors, which function as ligand-dependent, transacting regulatory proteins. Glucocorticoid receptor DNA-binding factor-1 (GRLF1) is thought to repress transcription of GCCR in response to glucocorticoids, thus damping the response of the liver to glucocorticoid stimulation (LeClerc et al., 1991).
Using polyclonal antibodies against purified GRLF1, LeClerc et al. (1991) isolated a partial GRLF1 cDNA encoding a deduced 835-amino acid protein. The protein contains 3 possible zinc finger structures and a leucine zipper motif that contains 1 cysteine. Western blot analysis detected expression of a 94-kD GRLF1 protein.
By sequence comparisons with rat p190A, database searching, and RT-PCR analysis, Tikoo et al. (2000) obtained a full-length cDNA sequence encoding GRLF1, the human homolog of p190A. The deduced 1,514-amino acid protein is 97% identical to the rat sequence. The first 1,287 residues, including the GTPase and middle domains, are encoded by the 3.7-kb exon 1, similar to the structure observed in p190B (ARHGAP5; 602680).
By Southwestern blot analysis and use of band shift assays with transfected COS-1 extracts, LeClerc et al. (1991) demonstrated that GRLF1 interacts with the GCCR promoter. They also showed that GRLF1 functions as a hormone-independent repressor of GCCR expression. They hypothesized that GRLF1 represses GCCR expression through direct interaction with a unique sequence in the GCCR regulatory region. Similar sequence motifs are found in the regulatory regions of the insulin receptor, androgen receptor, and c-myc genes.
In rats, LeClerc et al. (1991) observed a decrease in GRFL1 mRNA after adrenalectomy and a slight increase in the level of mRNA after subsequent glucocorticoid dexamethasone hormone treatment. The authors concluded that GRLF1 mRNA levels are regulated by glucocorticoids.
Wildenberg et al. (2006) found that depletion of delta-catenin (CTNND1; 601045) in NIH3T3 mouse fibroblasts by small interfering RNA caused constitutive activation of Rho, cell transformation, loss of contact inhibition, and growth in the absence of serum. Moreover, Pdgf receptor (see 173490) and integrin signaling pathways involved in remodeling the actin cytoskeleton were selectively impaired. Wildenberg et al. (2006) traced these effects to obligatory roles of delta-catenin and p190RhoGAP (Arhgap35) in a pathway that connects Rac activation to Rho inhibition. They concluded that delta-catenin and ARHGAP35 use Rho GTPases to mediate crosstalk between a wide variety of receptors to coordinate cadherin function with other activities that direct cell adhesion, motility, and proliferation.
Mammoto et al. (2009) showed that the Rho inhibitor p190RhoGAP (GRLF1) controls capillary network formation in vitro in human microvascular endothelial cells and retinal angiogenesis in vivo by modulating the balance of activities between 2 antagonistic transcription factors, TFII-I (GTF2I; 601679) and GATA2 (137295), that govern gene expression of the VEGF receptor VEGFR2 (191306). Moreover, this angiogenesis signaling pathway is sensitive to extracellular matrix elasticity as well as soluble VEGF. Mammoto et al. (2009) suggested that this finding represented the first known functional crossantagonism between transcription factors that controls tissue morphogenesis, and that responds to both mechanical and chemical cues.
By Southern blot analysis, Tikoo et al. (2000) determined that GRLF1 is a single-copy gene on chromosome 19. Using FISH and radiation hybrid analysis, they localized the GRLF1 gene to 19q13.2-q13.4, a region known to be altered in gliomas and pancreatic, ovarian, and thyroid tumors.
LeClerc, S., Palaniswami, R., Xie, B., Govdan, M. V.Molecular cloning and characterization of a factor that binds the human glucocorticoid receptor gene and represses its expression. J. Biol. Chem. 266: 17333-17340, 1991. [PubMed: 1894621]
Mammoto, A., Connor, K. M., Mammoto, T., Yung, C. W., Huh, D., Aderman, C. M., Mostoslavsky, G., Smith, L. E. H., Ingber, D. E.A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457: 1103-1108, 2009. [PubMed: 19242469] [Full Text: https://doi.org/10.1038/nature07765]
Tikoo, A., Czekay, S., Viars, C., White, S., Heath, J. K., Arden, K., Maruta, H.p190-A, a human tumor suppressor gene, maps to the chromosomal region 19q13.3 that is reportedly deleted in some gliomas. Gene 257: 23-31, 2000. [PubMed: 11054565] [Full Text: https://doi.org/10.1016/s0378-1119(00)00387-5]
Wildenberg, G. A., Dohn, M. R., Carnahan, R. H., Davis, M. A., Lobdell, N. A., Settleman, J., Reynolds, A. B.p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. Cell 127: 1027-1039, 2006. [PubMed: 17129786] [Full Text: https://doi.org/10.1016/j.cell.2006.09.046]
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