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Targeted deletion of the S-phase-specific Myc antagonist Mad3 sensitizes neuronal and lymphoid cells to radiation-induced apoptosis.

Quéva, C and McArthur, G A and Iritani, B M and Eisenman, R N (2001) Targeted deletion of the S-phase-specific Myc antagonist Mad3 sensitizes neuronal and lymphoid cells to radiation-induced apoptosis. Molecular and cellular biology, 21 (3). pp. 703-712. ISSN 0270-7306

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Article URL: http://mcb.asm.org/cgi/content/full/21/3/703

Abstract

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.

Item Type: Article
Additional Information: This article is freely available in PubMed Central and at the journal's website.
DOI: 10.1128/MCB.21.3.703-712.2001
PubMed ID: 11154258
PMCID: PMC86662
Grant Numbers: CA57138, HL54881, DRG-076, K08 AJ01445
Keywords or MeSH Headings: Animals; Apoptosis/genetics/physiology/radiation effects; Base Sequence; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cell Differentiation; Cell Division; DNA Primers/genetics; DNA-Binding Proteins/genetics/physiology; Gamma Rays; Gene Expression; Gene Targeting; Lymphocytes/cytology/radiation effects; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons/cytology/radiation effects; Proto-Oncogene Proteins c-myc/antagonists & inhibitors; Radiation Tolerance/drug effects/physiology; Repressor Proteins; S Phase/genetics/physiology;
Subjects: Molecules > Proteins > Transcription factors
Cellular and Organismal Processes > Cell Physiology > Cell death
Molecules > Genes > Oncogenes
Cellular and Organismal Processes > Cell Physiology > Cell cycle
Depositing User: Library Staff
Date Deposited: 25 Nov 2008 00:20
Last Modified: 07 May 2010 21:36
URI: http://authors.fhcrc.org/id/eprint/178

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