PMID: 9192873Jun 1, 1997Paper

Cyclin E-CDK2 is a regulator of p27Kip1

Genes & Development
R J SheaffB E Clurman

Abstract

CDK inhibitors are thought to prevent cell proliferation by negatively regulating cyclin-CDK complexes. We propose that the opposite is also true, that cyclin-CDK complexes in mammmalian cells can promote cell cycle progression by directly down-regulating CDK inhibitors. We show that expression of cyclin E-CDK2 in murine fibroblasts causes phosphorylation of the CDK inhibitor p27Kip1 on T187, and that cyclin E-CDK2 can directly phosphorylate p27 T187 in vitro. We further show that cyclin E-CDK2-dependent phosphorylation of p27 results in elimination of p27 from the cell, allowing cells to transit from G1 to S phase. Moreover, mutation of T187 in p27 to alanine creates a p27 protein that causes a G1 block resistant to cyclin E and whose level of expression is not modulated by cyclin E. A kinetic analysis of the interaction between p27 and cyclin E-CDK2 explains how p27 can be regulated by the same enzyme it targets for inhibition. We show that p27 interacts with cyclin E-CDK2 in at least two distinct ways: one resulting in p27 phosphorylation and release, the other in tight binding and cyclin E-CDK2 inhibition. The binding of ATP to the CDK governs which state predominates. At low ATP (< 50 microM) p27 is primarily a CDK inhibit...Continue Reading

References

Jan 1, 1987·Methods in Enzymology·T A KunkelR A Zakour
Jan 1, 1994·Cold Spring Harbor Symposia on Quantitative Biology·J M RobertsJ Massagué
May 15, 1995·Genes & Development·C J Sherr, J M Roberts
Mar 9, 1995·Nature·D O Morgan
Nov 18, 1994·Cell·C J Sherr
Nov 19, 1993·Cell·W S el-DeiryB Vogelstein
Dec 16, 1993·Nature·Y XiongD Beach
Dec 24, 1993·Science·S van den Heuvel, E Harlow
Apr 26, 1996·Science·B L SchneiderA B Futcher
Aug 1, 1996·Molecular and Cellular Biology·D AgrawalW J Pledger
Jul 1, 1996·Current Opinion in Hematology·B E ClurmanM Groudine

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Citations

Oct 1, 1965·Journal of Cellular Physiology·A Korner
Mar 4, 2000·Journal of Cellular Physiology·J Slingerland, M Pagano
Mar 4, 2000·Journal of Cellular Physiology·A SgambatoI B Weinstein
May 18, 2000·Reviews in Medical Virology·S Mittnacht, C Boshoff
Feb 27, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·K Nakayama, K Nakayama
Mar 10, 2001·Journal of Cellular Physiology·P R Yew
Jan 25, 2002·European Journal of Immunology·Rebecca J GreenwaldArlene H Sharpe
Jan 10, 2002·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Qing Qiu Pu, Charles H Streuli
Nov 28, 2002·International Journal of Cancer. Journal International Du Cancer·Daina Z EwtonEileen Friedman
May 16, 2001·Biochemical and Biophysical Research Communications·K I NakayamaK Nakayama
Feb 9, 2006·Cancer Chemotherapy and Pharmacology·Hironori IwasakiMasashi Inafuku
Jul 6, 2011·Journal of Molecular Neuroscience : MN·Xiujie WuJian Chen
Mar 16, 2013·Journal of Molecular Neuroscience : MN·Aihong LiXingxing Gu
Mar 24, 2004·Archives of Medical Research·Miguel CruzJesús Kumate
Jun 1, 2005·Biochemical and Biophysical Research Communications·Adam GeminGurmit Singh
May 19, 2004·The International Journal of Biochemistry & Cell Biology·Tarik Möröy, Christoph Geisen
Nov 24, 2005·Prostaglandins & Other Lipid Mediators·Devashish KothapalliRichard K Assoian
Apr 21, 2005·Seminars in Cell & Developmental Biology·Keiichi I Nakayama, Keiko Nakayama
Aug 9, 2003·Biochemical Pharmacology·Te-Hsiu LeeWen-Chun Hung
Jul 10, 2003·Fertility and Sterility·Rebecca L DubowyHarvey J Kliman
Sep 6, 2003·The Journal of Surgical Research·Klaus GüntherClaus Rödel
Jun 6, 2000·Brain Research. Molecular Brain Research·K SasakiT Hashimoto-Tamaoki
Jul 19, 2003·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Nesil KeleşKemal Değer
May 30, 2001·Molecular and Cellular Endocrinology·N Takuwa, Y Takuwa
Jun 2, 1998·Biochimica Et Biophysica Acta·S J Elledge, J W Harper
Jan 13, 1998·Current Opinion in Cell Biology·M D Planas-Silva, R A Weinberg
Jan 13, 1998·Current Opinion in Cell Biology·A Hershko
Feb 13, 2001·Current Opinion in Genetics & Development·R K Assoian, M A Schwartz
Apr 8, 1998·Current Opinion in Genetics & Development·S Mittnacht
Apr 8, 1998·Current Opinion in Genetics & Development·W Krek
Mar 11, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M D Garrett, P Workman
Aug 8, 1998·Trends in Cell Biology·C BouchardM Eilers
Apr 27, 1999·Trends in Biochemical Sciences·C SwantonN Jones

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