Spermatogenesis rescue in a mouse deficient for the ubiquitin ligase SCFβ-TrCP by single substrate depletion

Naama Kanarek, Elad Horwitz, Inbal Mayan, Michael Leshets, Gady Cojocaru, Matti Davis, Ben Zion Tsuberi, Eli Pikarsky, Michele Pagano, Yinon Ben-Neriah*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


β-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 β-TrCP hypomorphic mice and found that they are surprisingly healthy, yet have a severe testicular defect. We show that the two β-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 β-TrCP restoration. Remarkably, testicular depletion of a single β-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.

Original languageAmerican English
Pages (from-to)470-477
Number of pages8
JournalGenes and Development
Issue number5
StatePublished - 1 Mar 2010


  • Adherens junctions
  • SCF-E3
  • Snail1
  • Spermatogenesis
  • shRNA transgenic mouse
  • β-TrCP paralogs


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