Exclusion of germ plasm proteins from somatic lineages by cullin-dependent degradation

Nature. 2003 Aug 7;424(6949):685-9. doi: 10.1038/nature01887. Epub 2003 Jul 23.

Abstract

In many animals, establishment of the germ line depends on segregation of a specialized cytoplasm, or 'germ plasm', to a small number of germline precursor cells during early embryogenesis. Germ plasm asymmetry involves targeting of RNAs and proteins to a specific region of the oocyte and/or embryo. Here we demonstrate that germ plasm asymmetry also depends on degradation of germline proteins in non-germline (somatic) cells. We show that five CCCH finger proteins, components of the Caenorhabditis elegans germ plasm, are targeted for degradation by the novel CCCH-finger-binding protein ZIF-1. ZIF-1 is a SOCS-box protein that interacts with the E3 ubiquitin ligase subunit elongin C. Elongin C, the cullin CUL-2, the ring finger protein RBX-1 and the E2 ubiquitin conjugation enzyme UBC5 (also known as LET-70) are all required in vivo for CCCH finger protein degradation. Degradation is activated in somatic cells by the redundant CCCH finger proteins MEX-5 and MEX-6, which are counteracted in the germ line by the PAR-1 kinase. We propose that segregation of the germ plasm involves both stabilization of germline proteins in the germ line and cullin-dependent degradation in the soma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Lineage*
  • Cullin Proteins*
  • Cytoplasm / metabolism*
  • Elongin
  • Germ Cells / cytology*
  • Germ Cells / metabolism*
  • Ligases / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • RNA Interference
  • Transcription Factors / metabolism
  • Ubiquitin-Conjugating Enzymes*
  • Ubiquitin-Protein Ligases

Substances

  • CUL2 protein, human
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cullin Proteins
  • ELOC protein, human
  • Elongin
  • MEX-5 protein, C elegans
  • MEX-6 protein, C elegans
  • Transcription Factors
  • ZIF-1 protein, C elegans
  • Ubiquitin-Conjugating Enzymes
  • let-70 protein, C elegans
  • Ubiquitin-Protein Ligases
  • Ligases