Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-Myc protein is involved in cellular transformation and mitogenesis, but also works as a potent inducer of differentiation and programmed cell death. Max as an obligate heterodimeric partner for Myc mediates its functions as a specific transcriptional activator and a transforming protein. Mad and Mxi1 proteins both heterodimerize with Max and compete with each other for limiting amounts of Max. Transcriptional activation by Myc can be suppressed by increasing the amount of Mad or Mxi1. This report shows the expression pattern of these Myc related factors at the mRNA level in a small cell lung cancer (SCLC) cell line (GLC4) which is characterized by c-myc amplification and strong constitutive c-myc overexpression. We found these genes transcriptionally active but uninfluenced from high c-myc transcription. Max was constantly transcribed at a relatively low level during cell cycle progression. Mad and mxi1 mRNA was at a surprisingly high level in proliferating cells. Mad was further upregulated and mxi1 was downregulated to basal levels during serum starvation of the cells. We further analyzed the activity of c-fos, c-jun, c-myb and nm23 which are described to be involved in c-myc transcriptional activation, c-jun and c-fos were not constitutively activated and can be excluded as regulators. High steady state c-myc in contrast influences the serum stimulated transient activation mechanism of these two genes. We identified high copy number nm23 mRNA whose role as a putative c-myc transcriptional activator is under investigation. Our results indicate that constitutive overexpression of c-myc does not require the activity of the nuclear oncogenes tested and that the m-RNA expression pattern of functionally related proteins is not influenced.
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PMID:Coexpression pattern of c-myc associated genes in a small cell lung cancer cell line with high steady state c-myc transcription. 765 39

We examined the p53 status of 108 NSCLCs compared to the expression of MLH1 and MSH2 proteins. p53 overexpression was demonstrated by IHC in 64% of patients examined, whereas p53 mutations were detected in 43%. Twenty-two percent of mutations were located outside of the hot-spot (exons 5-8) area. p53 mutations and overexpression were more frequent in SCCL (57% and 73%, respectively) than in lung adenocarcinomas (22% and 50%, respectively). In NSCLC-carrying wild-type p53, increased expression of MSH2 correlated with p53 overexpression (p = 0.018). In addition, in SCCL, p53 mutations correlated with reduced MSH2 expression (p = 0.019). These data suggest a relationship between p53 and MSH2. While there is evidence for p53 being a transcriptional activator of MSH2, the hypothesis that MSH2 acts as a DNA-damage signaller triggering p53 overexpression needs to be clarified in future studies.
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PMID:p53 status correlates with the differential expression of the DNA mismatch repair protein MSH2 in non-small cell lung carcinoma. 1220 75