Spermatogenesis rescue in a mouse deficient for the ubiquitin ligase SCF{beta}-TrCP by single substrate depletion

Genes Dev. 2010 Mar 1;24(5):470-7. doi: 10.1101/gad.551610.


beta-TrCP, the substrate recognition subunit of a Skp1-Cul1-F-box (SCF) ubiquitin ligase, is ubiquitously expressed from two distinct paralogs, targeting many regulatory proteins for proteasomal degradation. We generated inducible beta-TrCP hypomorphic mice and found that they are surprisingly healthy, yet have a severe testicular defect. We show that the two beta-TrCP paralogs have a nonredundant role in spermatogenesis. The testicular defect is tightly associated with cell adhesion failure within the seminiferous tubules and is fully reversible upon beta-TrCP restoration. Remarkably, testicular depletion of a single beta-TrCP substrate, Snail1, rescued the adhesion defect and restored spermatogenesis. Our studies highlight an unexpected functional reserve of this central E3, as well as a bottleneck in a specific tissue: a single substrate whose stabilization is incompatible with testicular differentiation.

Publication types

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

MeSH terms

  • Animals
  • Intercellular Junctions / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Phenotype
  • Protein Isoforms
  • SKP Cullin F-Box Protein Ligases / genetics*
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Snail Family Transcription Factors
  • Spermatogenesis / physiology*
  • Testis / embryology*
  • Testis / pathology
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Protein Isoforms
  • Snai1 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factors
  • SKP Cullin F-Box Protein Ligases