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Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2

The decision for a cell to self-replicate requires passage from G1 to S phase of the cell cycle and initiation of another round of DNA replication. This commitment is a critical one that is tightly regulated by many parallel pathways. Significantly, these pathways converge to result in activation of...

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Autores principales: Porter, Lisa A., Dellinger, Ryan W., Tynan, John A., Barnes, Elizabeth A., Kong, Monica, Lenormand, Jean-Luc, Donoghue, Daniel J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173287/
https://www.ncbi.nlm.nih.gov/pubmed/11980914
http://dx.doi.org/10.1083/jcb.200109045
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author Porter, Lisa A.
Dellinger, Ryan W.
Tynan, John A.
Barnes, Elizabeth A.
Kong, Monica
Lenormand, Jean-Luc
Donoghue, Daniel J.
author_facet Porter, Lisa A.
Dellinger, Ryan W.
Tynan, John A.
Barnes, Elizabeth A.
Kong, Monica
Lenormand, Jean-Luc
Donoghue, Daniel J.
author_sort Porter, Lisa A.
collection PubMed
description The decision for a cell to self-replicate requires passage from G1 to S phase of the cell cycle and initiation of another round of DNA replication. This commitment is a critical one that is tightly regulated by many parallel pathways. Significantly, these pathways converge to result in activation of the cyclin-dependent kinase, cdk2. It is, therefore, important to understand all the mechanisms regulating cdk2 to determine the molecular basis of cell progression. Here we report the identification and characterization of a novel cell cycle gene, designated Speedy (Spy1). Spy1 is 40% homologous to the Xenopus cell cycle gene, X-Spy1. Similar to its Xenopus counterpart, human Speedy is able to induce oocyte maturation, suggesting similar biological characteristics. Spy1 mRNA is expressed in several human tissues and immortalized cell lines and is only expressed during the G1/S phase of the cell cycle. Overexpression of Spy1 protein demonstrates that Spy1 is nuclear and results in enhanced cell proliferation. In addition, flow cytometry profiles of these cells demonstrate a reduction in G1 population. Changes in cell cycle regulation can be attributed to the ability of Spy1 to bind to and prematurely activate cdk2 independent of cyclin binding. We demonstrate that Spy1-enhanced cell proliferation is dependent on cdk2 activation. Furthermore, abrogation of Spy1 expression, through the use of siRNA, demonstrates that Spy1 is an essential component of cell proliferation pathways. Hence, human Speedy is a novel cell cycle protein capable of promoting cell proliferation through the premature activation of cdk2 at the G1/S phase transition.
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spelling pubmed-21732872008-05-01 Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2 Porter, Lisa A. Dellinger, Ryan W. Tynan, John A. Barnes, Elizabeth A. Kong, Monica Lenormand, Jean-Luc Donoghue, Daniel J. J Cell Biol Article The decision for a cell to self-replicate requires passage from G1 to S phase of the cell cycle and initiation of another round of DNA replication. This commitment is a critical one that is tightly regulated by many parallel pathways. Significantly, these pathways converge to result in activation of the cyclin-dependent kinase, cdk2. It is, therefore, important to understand all the mechanisms regulating cdk2 to determine the molecular basis of cell progression. Here we report the identification and characterization of a novel cell cycle gene, designated Speedy (Spy1). Spy1 is 40% homologous to the Xenopus cell cycle gene, X-Spy1. Similar to its Xenopus counterpart, human Speedy is able to induce oocyte maturation, suggesting similar biological characteristics. Spy1 mRNA is expressed in several human tissues and immortalized cell lines and is only expressed during the G1/S phase of the cell cycle. Overexpression of Spy1 protein demonstrates that Spy1 is nuclear and results in enhanced cell proliferation. In addition, flow cytometry profiles of these cells demonstrate a reduction in G1 population. Changes in cell cycle regulation can be attributed to the ability of Spy1 to bind to and prematurely activate cdk2 independent of cyclin binding. We demonstrate that Spy1-enhanced cell proliferation is dependent on cdk2 activation. Furthermore, abrogation of Spy1 expression, through the use of siRNA, demonstrates that Spy1 is an essential component of cell proliferation pathways. Hence, human Speedy is a novel cell cycle protein capable of promoting cell proliferation through the premature activation of cdk2 at the G1/S phase transition. The Rockefeller University Press 2002-04-29 /pmc/articles/PMC2173287/ /pubmed/11980914 http://dx.doi.org/10.1083/jcb.200109045 Text en Copyright © 2002, 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 Article
Porter, Lisa A.
Dellinger, Ryan W.
Tynan, John A.
Barnes, Elizabeth A.
Kong, Monica
Lenormand, Jean-Luc
Donoghue, Daniel J.
Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2
title Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2
title_full Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2
title_fullStr Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2
title_full_unstemmed Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2
title_short Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2
title_sort human speedy: a novel cell cycle regulator that enhances proliferation through activation of cdk2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173287/
https://www.ncbi.nlm.nih.gov/pubmed/11980914
http://dx.doi.org/10.1083/jcb.200109045
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