Genome-wide analysis of germ cell proliferation in C.elegans identifies VRK-1 as a key regulator of CEP-1/p53

Dev Biol. 2010 Aug 15;344(2):1011-25. doi: 10.1016/j.ydbio.2010.06.022. Epub 2010 Jun 23.


Proliferating germ cells in Caenorhabditiselegans provide a useful model system for deciphering fundamental mechanisms underlying the balance between proliferation and differentiation. Using gene expression profiling, we identified approximately 200 genes upregulated in the proliferating germ cells of C. elegans. Functional characterization using RNA-mediated interference demonstrated that over forty of these factors are required for normal germline proliferation and development. Detailed analysis of two of these factors defined an important regulatory relationship controlling germ cell proliferation. We established that the kinase VRK-1 is required for normal germ cell proliferation, and that it acts in part to regulate CEP-1(p53) activity. Loss of cep-1 significantly rescued the proliferation defects of vrk-1 mutants. We suggest that VRK-1 prevents CEP-1 from triggering an inappropriate cell cycle arrest, thereby promoting germ cell proliferation. This finding reveals a previously unsuspected mechanism for negative regulation of p53 activity in germ cells to control proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans* / cytology
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / metabolism
  • Cell Cycle / genetics
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Gene Expression Profiling
  • Genes, p53
  • Genome
  • Germ Cells* / cytology
  • Germ Cells* / growth & development
  • Germ Cells* / metabolism
  • RNA Interference
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation


  • Tumor Suppressor Protein p53