Targeted Deletion of the S-Phase-Specific Myc Antagonist Mad3 Sensitizes Neuronal and Lymphoid Cells to Radiation-Induced Apoptosis
Copyright policy )Targeted Deletion of the S-Phase-Specific Myc Antagonist Mad3 Sensitizes Neuronal and Lymphoid Cells to Radiation-Induced Apoptosis
The Mad family comprises four basic-helix-loop-helix/leucine zipper proteins, Mad1, Mxi1, Mad3, and Mad4, which heterodimerize with Max and function as transcriptional repressors. The balance between Myc-Max and Mad-Max complexes has been postulated to influence cell proliferation and differentiation. The expression patterns of Mad family genes are complex, but in general, the induction of most family members is linked to cell cycle exit and differentiation. The expression pattern of mad3 is unusual in that mad3 mRNA and protein were found to be restricted to proliferating cells prior to differentiation. We show here that during murine development mad3 is specifically expressed in the S phase of the cell cycle in neuronal progenitor cells that are committed to differentiation. To investigate mad3 function, we disrupted the mad3 gene by homologous recombination in mice. No defect in cell cycle exit and differentiation could be detected in mad3 homozygous mutant mice. However, upon gamma irradiation, increased cell death of thymocytes and neural progenitor cells was observed, implicating mad3 in the regulation of the cellular response to DNA damage.
- Fred Hutchinson Cancer Research Center United States
- Fred Hutchinson Cancer Research Center South Africa
Cell death, Gene Expression, Apoptosis, Cell cycle, Radiation Tolerance, S Phase, Proto-Oncogene Proteins c-myc, Mice, Transcription factors, Animals, Lymphocytes, DNA Primers, Mice, Knockout, Neurons, Base Sequence, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cell Differentiation, Oncogenes, DNA-Binding Proteins, Mice, Inbred C57BL, Repressor Proteins, Gamma Rays, Gene Targeting, Cell Division
Cell death, Gene Expression, Apoptosis, Cell cycle, Radiation Tolerance, S Phase, Proto-Oncogene Proteins c-myc, Mice, Transcription factors, Animals, Lymphocytes, DNA Primers, Mice, Knockout, Neurons, Base Sequence, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cell Differentiation, Oncogenes, DNA-Binding Proteins, Mice, Inbred C57BL, Repressor Proteins, Gamma Rays, Gene Targeting, Cell Division
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).49 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!