In:
Genes & Development, Cold Spring Harbor Laboratory, Vol. 14, No. 24 ( 2000-12-15), p. 3093-3101
Abstract:
On TGF-β binding, the TGF-β receptor directly phosphorylates and activates the transcription factors Smad2/3, leading to G 1 arrest. Here, we present evidence for a second, parallel, TGF-β-dependent pathway for cell cycle arrest, achieved via inhibition of p70 s6k . TGF-β induces association of its receptor with protein phosphatase-2A (PP2A)-Bα. Concomitantly, three PP2A-subunits, Bα, Aβ, and Cα, associate with p70 s6k , leading to its dephosphorylation and inactivation. Although either pathway is sufficient to induce G 1 arrest, abrogation of both, the inhibition of p70 s6k , and transcription through Smad proteins is required for release of epithelial cells from TGF-β-induced G 1 arrest. TGF-β thereby modulates the translational and posttranscriptional control of cell cycle progression.
Type of Medium:
Online Resource
ISSN:
0890-9369
,
1549-5477
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2000
detail.hit.zdb_id:
1467414-2
SSG:
12
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