In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 19 ( 2007-05-08), p. 8047-8052
Abstract:
TRIF is an adaptor protein associated with the signaling by Toll-like receptor (TLR)3 and TLR4 for the induction of type I IFNs. Here, we demonstrate a mechanism by which TLR signaling controls cell proliferation and survival. We show that TLR3 and TLR4 can induce cell cycle entry via TRIF, which targets the cell cycle inhibitor p27 kip1 for relocalization, phosphorylation by cyclin/cdk complexes, and proteasome degradation. These events are antagonized by type I IFN induced by the TRIF pathway. Furthermore, in human dendritic cells treated with TLR3, TLR4, or TLR5 ligands, we demonstrate that IFN signaling modulates p27 kip1 degradation and apoptosis, identifying an immunoregulatory “switching” function of type I IFNs. These findings reveal a previously uncharacterized function of TLR signaling in cell proliferation and survival.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0700664104
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2007
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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