In:
Genes & Development, Cold Spring Harbor Laboratory, Vol. 24, No. 5 ( 2010-03-01), p. 470-477
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0890-9369
,
1549-5477
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2010
detail.hit.zdb_id:
1467414-2
SSG:
12
Permalink