Structure and Chromosomal Localization of Mouse G Protein Subunit γ4 Gene

Kalyanaraman, S.; Copeland, Neal G.; Gilbert, David; Jenkins, Nancy A.; Gautam, N.

doi:10.1006/geno.1998.5223

Cited by 17 publications

(12 citation statements)

References 26 publications

(3 reference statements)

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“…It has been suggested that increased rates of proliferation and levels of malignancy in colorectal tumour cells may be attributable to downregulation of one or more isoforms of GLS, accompanied by increased glucose metabolism (Turner and McGivan, 2003). GNG4 is a member of the G protein gamma subunits multigene family (Kleuss et al, 1993), which is required for coupling of the muscarinic receptor to voltage-sensitive calcium channels (Kalyanaraman et al, 1998). To investigate whether GNG4 has tumour suppressor activity, we transformed wild-type GNG4 into a RCC cell line with loss of GNG4 expression.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel VHL target genes and relationship to hypoxic response pathways

et al. 2005

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Upregulation of hypoxia-inducible factors HIF-1 and HIF-2 is frequent in human cancers and may result from tissue hypoxia or genetic mechanisms, in particular the inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene (TSG). Tumours with VHL inactivation are highly vascular, but it is unclear to what extent HIFdependent and HIF-independent mechanisms account for pVHL tumour suppressor activity. As the identification of novel pVHL targets might provide insights into pVHL tumour suppressor activity, we performed gene expression microarray analysis in VHL-wild-type and VHL-null renal cell carcinoma (RCC) cell lines. We identified 30 differentially regulated pVHL targets (26 of which were 'novel') and the results of microarray analysis were confirmed in all 11 novel targets further analysed by real-time RT-PCR or Western blotting. Furthermore, nine of 11 targets were dysregulated in the majority of a series of primary clear cell RCC with VHL inactivation. Three of the nine targets had been identified previously as candidate TSGs (DOC-2/DAB2, CDKN1C and SPARC) and all were upregulated by wild-type pVHL. The significance for pVHL function of two further genes upregulated by wild-type pVHL was initially unclear, but re-expression of GNG4 (G protein gamma-4 subunit/ guanine nucleotide-binding protein-4) and MLC2 (myosin light chain) in a RCC cell line suppressed tumour cell growth. pVHL regulation of CDKN1C, SPARC and GNG4 was not mimicked by hypoxia, whereas for six of 11 novel targets analysed (including DOC-2/DAB2 and MLC2) the effects of pVHL inactivation and hypoxia were similar. For GPR56 there was evidence of a tissuespecific hypoxia response. Such a phenomenon might, in part, explain organ-specific tumorigenesis in VHL disease. These provide insights into mechanisms of pVHL tumour suppressor function and identify novel hypoxiaresponsive targets that might be implicated in tumorigenesis in both VHL disease and in other cancers with HIF upregulation.

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Section: Discussionmentioning

confidence: 99%

Identification of novel VHL target genes and relationship to hypoxic response pathways

et al. 2005

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“…Most of the ␤ and ␥ subunit genes have also been mapped (1,19,30,38,64,72,87) (Table 4). These genes are well dispersed in both the mouse and the human genomes with the exception of a tandem pair of ␥ subunit genes-the GNGT1 (␥1) and GNG11 (␥11) genes (AC002076).…”

Section: Organization Of the G Protein Subunit Genes In Mammalian Genmentioning

confidence: 98%

“…Additional interest in the ␣ subunit genes was stimulated by the discovery of mutations in these genes associated with human disease (76). In the past few years, several genes for the ␤ and ␥ subunits have also been identified and characterized (18,19,22,38,64,73,80). Information about these three gene families has also come from the large-scale human and mouse genome sequencing efforts.…”

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confidence: 97%

The G Protein Subunit Gene Families

1999

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“…In mouse, the map positions for ␥3 and ␥4 have been reported by us, and the map position of ␥7 has been reported by Danielson et al (6;see also Refs. 7,14). Here, we report the chromosomal location of five additional ␥ subunits within the mouse genome: ␥c, ␥2, ␥8, ␥10, and ␥12.…”

mentioning

confidence: 90%

“…Gng3 maps to chromosome 19 (7), Gng4 maps to chromosome 13 (14), and Gng7 maps to chromosome 10 (6). Although the three remaining ␥ subunits were not successfully mapped within the mouse genome, these genes, GngT1 (which encodes ␥1), Gng5, and Gng11, have been mapped within the human genome.…”

mentioning

confidence: 99%