c-myc box II mutations in Burkitt's lymphoma-derived alleles reduce cell-transformation activity and lower response to broad apoptotic stimuli

Fabien Kuttler, Patricia Amé, Helen Clark, Claudine Haughey, Christiane Mougin, Jean Yves Cahn, Chi V. Dang, Mark Raffeld, Thierry Fest

Research output: Contribution to journalArticlepeer-review

Abstract

In addition to c-myc rearrangement, over 50% of Burkitt's lymphoma cases present clustered mutations in exon 2, where many of the functional activities of c-Myc protein are based. This report describes the functional consequences induced by tumour-derived c-myc mutations located in c-myc box II. Two mutated alleles were studied, focusing on the P138C mutation, and compared to wild-type c-myc. The c-Myc transformation, transactivation and apoptosis activities were explored based on cells over-expressing c-Myc. While the transcriptional activation activity was not affected, our experiments exploring the anchorage-independent growth capacity of c-Myc-transfected Ratla cells showed that c-Myc box II mutants were less potent than wild-type c-Myc in promoting cell transformation. Considering the possibility that these mutations could be interfering with the ability of c-Myc to promote apoptosis, we tested c-Myc-transfected Ratla fibroblasts under several conditions: serum deprivation-, staurosporine- and TNFα-induced cell death. Interestingly, the mutated alleles were characterized by an overall decrease in ability to mediate apoptosis. Our study indicates that point mutations located in c-Myc box II can decrease the ability of the protein to promote both transformation and apoptosis without modifying its transactivating activity.

Original languageEnglish (US)
Pages (from-to)6084-6094
Number of pages11
JournalOncogene
Volume20
Issue number42
DOIs
StatePublished - Sep 20 2001

Keywords

  • Apoptosis
  • Burkitt's lymphoma
  • c-Myc
  • Staurosporine
  • TNFα

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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