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A Skp2 autoinduction loop and restriction point control
We describe a self-amplifying feedback loop that autoinduces Skp2 during G1 phase progression. This loop, which contains Skp2 itself, p27(kip1) (p27), cyclin E–cyclin dependent kinase 2, and the retinoblastoma protein, is closed through a newly identified, conserved E2F site in the Skp2 promoter. In...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064539/ https://www.ncbi.nlm.nih.gov/pubmed/17724117 http://dx.doi.org/10.1083/jcb.200703034 |
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author | Yung, Yuval Walker, Janice L. Roberts, James M. Assoian, Richard K. |
author_facet | Yung, Yuval Walker, Janice L. Roberts, James M. Assoian, Richard K. |
author_sort | Yung, Yuval |
collection | PubMed |
description | We describe a self-amplifying feedback loop that autoinduces Skp2 during G1 phase progression. This loop, which contains Skp2 itself, p27(kip1) (p27), cyclin E–cyclin dependent kinase 2, and the retinoblastoma protein, is closed through a newly identified, conserved E2F site in the Skp2 promoter. Interference with the loop, by knockin of a Skp2-resistant p27 mutant (p27(T187A)), delays passage through the restriction point but does not interfere with S phase entry under continuous serum stimulation. Skp2 knock down inhibits S phase entry in nontransformed mouse embryonic fibroblasts but not in human papilloma virus–E7 expressing fibroblasts. We propose that the essential role for Skp2-dependent degradation of p27 is in the formation of an autoinduction loop that selectively controls the transition to mitogen-independence, and that Skp2-dependent proteolysis may be dispensable when pocket proteins are constitutively inactivated. |
format | Text |
id | pubmed-2064539 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20645392008-02-27 A Skp2 autoinduction loop and restriction point control Yung, Yuval Walker, Janice L. Roberts, James M. Assoian, Richard K. J Cell Biol Research Articles We describe a self-amplifying feedback loop that autoinduces Skp2 during G1 phase progression. This loop, which contains Skp2 itself, p27(kip1) (p27), cyclin E–cyclin dependent kinase 2, and the retinoblastoma protein, is closed through a newly identified, conserved E2F site in the Skp2 promoter. Interference with the loop, by knockin of a Skp2-resistant p27 mutant (p27(T187A)), delays passage through the restriction point but does not interfere with S phase entry under continuous serum stimulation. Skp2 knock down inhibits S phase entry in nontransformed mouse embryonic fibroblasts but not in human papilloma virus–E7 expressing fibroblasts. We propose that the essential role for Skp2-dependent degradation of p27 is in the formation of an autoinduction loop that selectively controls the transition to mitogen-independence, and that Skp2-dependent proteolysis may be dispensable when pocket proteins are constitutively inactivated. The Rockefeller University Press 2007-08-27 /pmc/articles/PMC2064539/ /pubmed/17724117 http://dx.doi.org/10.1083/jcb.200703034 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Yung, Yuval Walker, Janice L. Roberts, James M. Assoian, Richard K. A Skp2 autoinduction loop and restriction point control |
title | A Skp2 autoinduction loop and restriction point control |
title_full | A Skp2 autoinduction loop and restriction point control |
title_fullStr | A Skp2 autoinduction loop and restriction point control |
title_full_unstemmed | A Skp2 autoinduction loop and restriction point control |
title_short | A Skp2 autoinduction loop and restriction point control |
title_sort | skp2 autoinduction loop and restriction point control |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064539/ https://www.ncbi.nlm.nih.gov/pubmed/17724117 http://dx.doi.org/10.1083/jcb.200703034 |
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