Mitogenic effects of the proto-oncogene and oncogene forms of c-H-ras DNA in human diploid fibroblasts.

Lumpkin, Charles K.; Knepper, Janice E.; Butel, Janet S.; Smith, James R.; Pereira‐Smith, Olivia M.

doi:10.1128/mcb.6.8.2990

Cited by 36 publications

(16 citation statements)

References 37 publications

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“…Assuming that these differences in expression correlate with the levels of gene product, our results are in agreement with the current thought that the cellular functions of the p2ls encoded by H-ras, K-ras, and N-ras are indeed different, as their products seem to be required in different amounts and at different times in a tissue-specific manner. Although p21 seems to be involved in cell proliferation (23,27), in this study we showed that H-ras is also expressed in mouse brain and muscle at its highest levels, where cell division is minimal. This suggests a role for ras genes which is not restricted to proliferation.…”

mentioning

confidence: 82%

Differential expression of the ras gene family in mice.

León¹,

Guerrero²,

Pellicer³

1987

Mol. Cell. Biol.

204

143

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We compared the expression of the ras gene family (H-ras, K-ras, and N-ras) in adult mouse tissues and during development. We found substantial variations in expression among different organs and in the amounts of the different transcripts originating from each gene, especially for the N-ras gene. The expression patterns were consistent with the reported preferential tissue activation of ras genes and suggested different cellular functions for each of the ras genes.

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mentioning

confidence: 82%

Differential expression of the ras gene family in mice.

León¹,

Guerrero²,

Pellicer³

1987

Mol. Cell. Biol.

204

143

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“…H-ras protein can induce DNA synthesis (21) or differentiation (1) in different cell types. In Xenopus oocytes, ras protein can induce meiosis (2).…”

Section: Discussionmentioning

confidence: 99%

The ras-like yeast YPT1 gene is itself essential for growth, sporulation, and starvation response.

Segev¹,

Botstein²

1987

Mol. Cell. Biol.

114

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The Saccharomyces cerevisiae gene YPTI encodes a protein that exhibits significant homology to the mammalian ras proteins. Using gene disruption techniques, we have shown that the intact YPTI gene is required for spore viability. Lethality caused by loss of YPTI function, unlike that caused by loss of the yeast ras homologs RAS] and RAS2 function, is not suppressed by the bcyl mutation, suggesting that YPTI does not act through the adenylate cyclase regulatory system. A cold-sensitive allele, yptl-1, was constructed. At the nonpermissive temperature, mutants died, exhibiting aberrant nuclear morphology, as well as abnormal distribution of actin and tubulin. The mutant cells died without exhibiting classical cell-cycle-specific arrest; nevertheless, examination of cellular DNA content suggests that the YPTI function is required, particularly after S phase. Cells carrying the yptl-l mutation died upon nitrogen starvation even at a temperature permissive for growth; diploid cells homozygous for yptl-l did not sporulate. The YPTI gene is thus involved in nutritional regulation of the cell cycle as well as in normal progression through the mitotic ceDl cycle.

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“…Log-phase, quiescent, and senescent HCA2 ( foreskinderived fibroblast, also called MJ90) and IMR90 (lung-derived fibroblast) cells were cultured as described previously (19). Confluent cultures of young cells, population doubling (PD) 34 or lower, were made quiescent by incubation in 1% serum-containing medium for at least 7 days, conditions we have established previously and have confirmed typically result in <15% cells labeling after a 48-hour continuous bromodeoxyuridine exposure.…”

Section: Methodsmentioning

confidence: 99%

p53 Is Preferentially Recruited to the Promoters of Growth Arrest Genes p21 and GADD45 during Replicative Senescence of Normal Human Fibroblasts

2006

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Replicative senescence is the terminal growth arrest that most normal human cells enter into after a fixed number of divisions in vitro, limiting the proliferative potential of a cell and preventing genomic instability caused by critically short telomeres. Thus, senescence presents a tumor-suppressive mechanism and a barrier to tumor formation. However, senescent cells are inherently resistant to apoptosis and, as they accumulate in aging tissues, may contribute to organ dysfunction and promote tumor progression as part of the stromal environment. Replicative life span in normal human cells can be extended by inactivation of the tumor suppressor gene p53 or its direct target, the cyclin-dependent kinase inhibitor p21, suggesting a direct role for this pathway in senescence. However, p53 recruitment to promoters of target genes during replicative senescence has not been shown in live cells. In this study, we used chromatin immunoprecipitation to determine that p53 preferentially occupied the promoters of growth arrest genes p21 and GADD45 in senescent normal human diploid fibroblasts but not the promoters of other target genes that recruited p53 following doxorubicin-induced DNA damage, such as apoptosis regulators TNFRSF10b, TNFRSF6, and PUMA. This differential recruitment of p53 in senescent versus doxorubicin-treated fibroblasts was accompanied by differences in post-translational modification of p53. These data provide mechanisms for both the growth arrest mediated by p53 and the resistant nature of senescent cells to apoptosis despite p53 activity.

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Mitogenic effects of the proto-oncogene and oncogene forms of c-H-ras DNA in human diploid fibroblasts.

Cited by 36 publications

References 37 publications

Differential expression of the ras gene family in mice.

Differential expression of the ras gene family in mice.

The ras-like yeast YPT1 gene is itself essential for growth, sporulation, and starvation response.

p53 Is Preferentially Recruited to the Promoters of Growth Arrest Genes p21 and GADD45 during Replicative Senescence of Normal Human Fibroblasts

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