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Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network.
Cell Death Differ. 2007 Apr; 14(4):662-70.CD

Abstract

Caenorhabditis elegans CEP-1 activates germline apoptosis in response to genotoxic stress, similar to its mammalian counterpart, tumor suppressor p53. In mammals, there are three p53 family members (p53, p63, and p73) that activate and repress many distinct and overlapping sets of genes, revealing a complex transcriptional regulatory network. Because CEP-1 is the sole p53 family member in C. elegans, analysis of this network is greatly simplified in this organism. We found that CEP-1 functions during normal development in the absence of stress to repress many (331) genes and activate only a few (28) genes. In response to genotoxic stress, 1394 genes are activated and 942 are repressed, many of which contain p53-binding sites. Comparison of the CEP-1 transcriptional network with transcriptional targets of the human p53 family reveals considerable overlap between CEP-1-regulated genes and homologues regulated by human p63 and p53, suggesting a composite p53/p63 action for CEP-1. We found that phg-1, the C. elegans Gas1 (growth arrest-specific 1) homologue, is activated by CEP-1 and is a negative regulator of cell proliferation in the germline in response to genotoxic stress. Further, we find that CEP-1 and PHG-1 mediate the decreased developmental rate and embryonic viability of mutations in the clk-2/TEL2 gene, which regulates lifespan and checkpoint responses.

Authors+Show Affiliations

Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA. brent.derry@sickkids.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17186023

Citation

Derry, W B., et al. "Regulation of Developmental Rate and Germ Cell Proliferation in Caenorhabditis Elegans By the P53 Gene Network." Cell Death and Differentiation, vol. 14, no. 4, 2007, pp. 662-70.
Derry WB, Bierings R, van Iersel M, et al. Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network. Cell Death Differ. 2007;14(4):662-70.
Derry, W. B., Bierings, R., van Iersel, M., Satkunendran, T., Reinke, V., & Rothman, J. H. (2007). Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network. Cell Death and Differentiation, 14(4), 662-70.
Derry WB, et al. Regulation of Developmental Rate and Germ Cell Proliferation in Caenorhabditis Elegans By the P53 Gene Network. Cell Death Differ. 2007;14(4):662-70. PubMed PMID: 17186023.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network. AU - Derry,W B, AU - Bierings,R, AU - van Iersel,M, AU - Satkunendran,T, AU - Reinke,V, AU - Rothman,J H, Y1 - 2006/12/22/ PY - 2006/12/23/pubmed PY - 2007/7/25/medline PY - 2006/12/23/entrez SP - 662 EP - 70 JF - Cell death and differentiation JO - Cell Death Differ VL - 14 IS - 4 N2 - Caenorhabditis elegans CEP-1 activates germline apoptosis in response to genotoxic stress, similar to its mammalian counterpart, tumor suppressor p53. In mammals, there are three p53 family members (p53, p63, and p73) that activate and repress many distinct and overlapping sets of genes, revealing a complex transcriptional regulatory network. Because CEP-1 is the sole p53 family member in C. elegans, analysis of this network is greatly simplified in this organism. We found that CEP-1 functions during normal development in the absence of stress to repress many (331) genes and activate only a few (28) genes. In response to genotoxic stress, 1394 genes are activated and 942 are repressed, many of which contain p53-binding sites. Comparison of the CEP-1 transcriptional network with transcriptional targets of the human p53 family reveals considerable overlap between CEP-1-regulated genes and homologues regulated by human p63 and p53, suggesting a composite p53/p63 action for CEP-1. We found that phg-1, the C. elegans Gas1 (growth arrest-specific 1) homologue, is activated by CEP-1 and is a negative regulator of cell proliferation in the germline in response to genotoxic stress. Further, we find that CEP-1 and PHG-1 mediate the decreased developmental rate and embryonic viability of mutations in the clk-2/TEL2 gene, which regulates lifespan and checkpoint responses. SN - 1350-9047 UR - https://www.unboundmedicine.com/medline/citation/17186023/Regulation_of_developmental_rate_and_germ_cell_proliferation_in_Caenorhabditis_elegans_by_the_p53_gene_network_ L2 - https://doi.org/10.1038/sj.cdd.4402075 DB - PRIME DP - Unbound Medicine ER -