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• W2137945427 abstract "Dergulation of c-myc and mutation of ras genes is commonly found in many human tumors. Several lines of evidence indicate that c-Myc and oncogenic Ras cooperate in causing malignant transformation, but the mechanism of this cooperation is not understood. We set out to investigate the effect on transformation of a modest reduction in endogenous c-Myc expression, which was achieved using a c-myc heterozygous cell line constructed by targeted homologous recombination. In contrast to previous reports where c-Myc expression or activity was ablated using antisense or dominant-defective methods, use of c-myc +/- cells provides a stable and homogeneous cell culture system with a precisely defined c-Myc expression level. In addition, this approach does not suffer from nonspecific artifacts such as antisense oligonucleotide toxicity or interference of dominant-defective proteins with multiple (and often undefined) target proteins. The striking and unexpected finding communicated here is that the relatively modest 50% reduction in c-Myc expression resulted in a greater than 10-fold reduction in susceptibility to transformation by oncogenic Ras or Raf proteins. This very significant defect in transformation potential cannot be explained on the basis of a generalized cell-cycle defect, because c-myc +/- cells exhibit only a minimal (20%) reduction in proliferation. Genetic epistasis analysis indicated that c-Myc and Ras acted by independent pathways that converged to regulate the abundance of the cyclin-dependent kinase inhibitor protein p27Kip1. Anchorage deprivation elicited a strong up-regulation of p27, and a 50% reduction in c-Myc expression significantly compromised the ability of Ras to down-regulate p27. We propose that Ras and c-Myc signals cooperate to regulate the activity of cyclin D-Cdk4/6 complexes: the former by up-regulating the expression of cyclin D1 and the latter by affecting the activity of the complexes. Ectopic expression of cyclin A restored the transformation potential of c-myc +/- cells, implicating it as a downstream genetic component in the pathway. From a therapeutic standpoint, it is of interest that, although transformation appears to be very sensitive to c-Myc expression levels, much larger reductions can be tolerated without causing any significant cell cycle defects." @default.
• W2137945427 created "2016-06-24" @default.
• W2137945427 creator A5015828322 @default.
• W2137945427 creator A5037220864 @default.
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• W2137945427 creator A5072685369 @default.
• W2137945427 creator A5081797261 @default.
• W2137945427 creator A5087202055 @default.
• W2137945427 date "2001-02-01" @default.
• W2137945427 modified "2023-09-26" @default.
• W2137945427 title "A modest reduction in c-myc expression has minimal effects on cell growth and apoptosis but dramatically reduces susceptibility to Ras and Raf transformation." @default.
• W2137945427 cites W1481295510 @default.
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• W2137945427 cites W1509850974 @default.
• W2137945427 cites W1520658182 @default.
• W2137945427 cites W1537459781 @default.
• W2137945427 cites W1538028541 @default.
• W2137945427 cites W1545398558 @default.
• W2137945427 cites W1547608553 @default.
• W2137945427 cites W1559682240 @default.
• W2137945427 cites W1576746816 @default.
• W2137945427 cites W1805917608 @default.
• W2137945427 cites W1860728469 @default.
• W2137945427 cites W1906271222 @default.
• W2137945427 cites W1949052814 @default.
• W2137945427 cites W1966453709 @default.
• W2137945427 cites W1971254046 @default.
• W2137945427 cites W1971657539 @default.
• W2137945427 cites W1974614531 @default.
• W2137945427 cites W1976655304 @default.
• W2137945427 cites W1980855212 @default.
• W2137945427 cites W1994441429 @default.
• W2137945427 cites W2002257918 @default.
• W2137945427 cites W2002761352 @default.
• W2137945427 cites W2004794055 @default.
• W2137945427 cites W2010307195 @default.
• W2137945427 cites W2011348663 @default.
• W2137945427 cites W2012731204 @default.
• W2137945427 cites W2012850212 @default.
• W2137945427 cites W2017551357 @default.
• W2137945427 cites W2021457628 @default.
• W2137945427 cites W2023887187 @default.
• W2137945427 cites W2030618323 @default.
• W2137945427 cites W2033060201 @default.
• W2137945427 cites W2035641694 @default.
• W2137945427 cites W2036216798 @default.
• W2137945427 cites W2039074795 @default.
• W2137945427 cites W2040848280 @default.
• W2137945427 cites W2041573061 @default.
• W2137945427 cites W2044312503 @default.
• W2137945427 cites W2063753069 @default.
• W2137945427 cites W2068842251 @default.
• W2137945427 cites W2070556283 @default.
• W2137945427 cites W2079494240 @default.
• W2137945427 cites W2081638226 @default.
• W2137945427 cites W2081948388 @default.
• W2137945427 cites W2083254800 @default.
• W2137945427 cites W2087404852 @default.
• W2137945427 cites W2089921110 @default.
• W2137945427 cites W2091444169 @default.
• W2137945427 cites W2094657382 @default.
• W2137945427 cites W2096657295 @default.
• W2137945427 cites W2098148985 @default.
• W2137945427 cites W2104014517 @default.
• W2137945427 cites W2105896701 @default.
• W2137945427 cites W2108559706 @default.
• W2137945427 cites W2114586401 @default.
• W2137945427 cites W2116500217 @default.
• W2137945427 cites W2122054853 @default.
• W2137945427 cites W2125255467 @default.
• W2137945427 cites W2126901946 @default.
• W2137945427 cites W2130026994 @default.
• W2137945427 cites W2154083290 @default.
• W2137945427 cites W2154169742 @default.
• W2137945427 cites W2161762726 @default.
• W2137945427 cites W2165712565 @default.
• W2137945427 cites W2167150841 @default.
• W2137945427 cites W2316297264 @default.
• W2137945427 cites W2330234900 @default.
• W2137945427 cites W2395527185 @default.
• W2137945427 cites W2413566119 @default.
• W2137945427 cites W2416591984 @default.
• W2137945427 cites W2475105307 @default.
• W2137945427 cites W35370265 @default.
• W2137945427 cites W569951484 @default.
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• W2137945427 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11221849" @default.
• W2137945427 hasPublicationYear "2001" @default.
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