In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 15 ( 2003-07-22), p. 8752-8757
Abstract:
β-TrCP1 (also known as Fbw1a or FWD1) is the F-box protein component
of an Skp1/Cul1/F-box (SCF)-type ubiquitin ligase complex. Although biochemical studies have suggested that β-TrCP1 targets inhibitory
subunit of NF-κB(IκB) proteins and β-catenin for ubiquitylation, the physiological role of β-TrCP1 in mammals has remained
unclear. We have now generated mice deficient in β-TrCP1 and shown that the degradation of IκBα and IκBβ is reproducibly, but
not completely, impaired in the cells of these animals. The nuclear translocation and DNA-binding activity of NF-κB as well as the ability
of this transcription factor to activate a luciferase reporter gene were also inhibited in β-TrCP1 – / – cells compared with those apparent in wild-type cells. The subcellular
localization of β-catenin was altered markedly in β-TrCP1 – / – cells.
Furthermore, the rate of proliferation was reduced and both cell size and the percentage of polyploid cells were increased in embryonic fibroblasts derived
from β-TrCP1 – / – mice pared
with the corresponding wild-type cells. These results suggest that β-TrCP1 contributes to, but is not absolutely required for, the
degradation of IκB and β-catenin and the consequent regulation of the NF-κB and Wnt signaling pathways, respectively. In addition, they
implicate β-TrCP1 in the maintenance of ploidy during cell-cycle progression.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1133216100
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2003
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
