Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network

W B Derry1, R Bierings, M van Iersel

  • 1Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106, USA. brent.derry@sickkids.ca

Insights

Caenorhabditis elegans CEP-1, a tumor suppressor, regulates gene expression during development and in response to genotoxic stress. Its network overlaps with human p53/p63, suggesting conserved functions in cell cycle control.

Area of Science:

  • Genetics
  • Molecular Biology
  • Developmental Biology

Background:

  • The tumor suppressor p53 and its family members (p53, p63, p73) regulate complex gene networks in mammals.
  • Caenorhabditis elegans possesses a single p53 family member, CEP-1, simplifying the study of p53-mediated transcriptional regulation.

Purpose of the Study:

  • To elucidate the transcriptional network regulated by CEP-1 in Caenorhabditis elegans during normal development and in response to genotoxic stress.
  • To compare the CEP-1 transcriptional network with human p53 family targets to infer conserved functions.

Main Methods:

  • Transcriptome analysis to identify genes regulated by CEP-1 under normal and stress conditions.
  • Bioinformatic comparison of CEP-1 target genes with human p53/p63 regulated genes.
  • Functional analysis of CEP-1 and its target gene phg-1 in response to genotoxic stress and clk-2/TEL2 mutations.

Main Results:

  • CEP-1 represses 331 genes and activates 28 genes during normal development.
  • Genotoxic stress leads to CEP-1-mediated activation of 1394 genes and repression of 942 genes.
  • CEP-1 regulates genes homologous to those targeted by human p53 and p63, indicating a composite function.
  • CEP-1 activates phg-1, a negative regulator of germline proliferation.
  • CEP-1 and PHG-1 influence developmental rate and viability in clk-2/TEL2 mutants.

Conclusions:

  • CEP-1 functions as a broader transcriptional regulator than previously appreciated, impacting both development and stress response.
  • The CEP-1 network shares significant overlap with human p53/p63 targets, suggesting conserved roles in cellular regulation.
  • CEP-1 and its target PHG-1 play crucial roles in germline integrity and response to DNA damage, linking to lifespan and checkpoint pathways.

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