Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-beta in cells lacking the CDK inhibitor p15

Nature
A Iavarone, J Massagué

Abstract

The activity of the cyclin-dependent kinases (CDKs) that control cell growth and division can be negatively regulated by tyrosine phosphorylation or by the binding of various CDK inhibitors. Whereas regulation by tyrosine phosphorylation is well documented in CDKs that function during mitosis, little is known about its role in the regulation of CDKs that act in the G1 phase of the cell cycle. In contrast, much evidence has accumulated on the regulation of G1 CDKs by CDK inhibitors. The cytokine TGF-beta inhibits growth by causing cell-cycle arrest as a result of increasing the concentration of the Cdk4/6 inhibitor p15(INK4B/MTS2) (refs 3, 4). Here we report that TGF-beta can also cause the inhibition of Cdk4 and Cdk6 by increasing their level of tyrosine phosphorylation. Tyrosine phosphorylation and inactivation of Cdk4/6 in a human mammary epithelial cell line are shown to result from the ability of TGF-beta to repress expression of the CDK tyrosine phosphatase Cdc25A. Repression of Cdc25A and induction of p15 are independent effects mediating the inhibition of Cdk4/6 by TFG-beta.

References

Mar 1, 1988·The Journal of Cell Biology·P BoukampN E Fusenig
Nov 21, 1995·Proceedings of the National Academy of Sciences of the United States of America·A SchulzeB Henglein
Sep 15, 1995·Science·K GalaktionovD Beach
May 15, 1995·Genes & Development·C J Sherr, J M Roberts
Mar 9, 1995·Nature·D O Morgan
Mar 1, 1994·Molecular and Cellular Biology·H MatsushimeJ Y Kato
Mar 1, 1994·Molecular and Cellular Biology·M Meyerson, E Harlow
Dec 24, 1993·Science·S van den Heuvel, E Harlow
Aug 8, 1996·Nature·K GalaktionovD Beach

❮ Previous
Next ❯

Citations

May 26, 1999·The Journal of Pathology·R J Akhurst, A Balmain
Mar 17, 1999·International Journal of Cancer. Journal International Du Cancer·F Pouliot, C Labrie
Feb 15, 2001·Microscopy Research and Technique·J RichX Wang
Dec 18, 2001·International Journal of Cancer. Journal International Du Cancer·M YoshidaT Ikekawa
Mar 29, 2002·Journal of Cellular Physiology·Peter Ten DijkeSusumu Itoh
Oct 12, 2012·Apoptosis : an International Journal on Programmed Cell Death·Cristina BarditaSanda Predescu
Mar 17, 2006·Breast Cancer Research and Treatment·Abde M AbukhdeirBen Ho Park
Jul 27, 2012·Cancer Metastasis Reviews·Stephen DouglassJohn A Kirby
May 19, 2004·The International Journal of Biochemistry & Cell Biology·Tarik Möröy, Christoph Geisen
Feb 13, 2003·Journal of Molecular Biology·Brian I CarrJohn S Lazo
May 30, 2001·Mutation Research·S JinnoH Okayama
Nov 15, 2001·Pharmacology & Therapeutics·J Yue, K M Mulder
Apr 19, 2002·Biochimica Et Biophysica Acta·Sagrario OrtegaMariano Barbacid
Nov 21, 1998·Biochimica Et Biophysica Acta·M Ruas, G Peters
Feb 19, 2002·International Journal of Radiation Oncology, Biology, Physics·Anu GuptaLing chun Chen
Nov 7, 2000·Current Opinion in Cell Biology·S V Ekholm, S I Reed
Jan 13, 1998·Current Opinion in Cell Biology·M D Planas-Silva, R A Weinberg
Apr 8, 1998·Current Opinion in Genetics & Development·S Mittnacht
Feb 23, 2002·Trends in Cell Biology·Mathieu Bollen, Monique Beullens
Dec 28, 1999·Microbes and Infection·M Reiss
Apr 20, 2001·Cytokine & Growth Factor Reviews·X LiuH F Lodish
Feb 23, 2013·Cell Death and Differentiation·T BerteroR Rezzonico
Apr 15, 2000·Cell Research·D Donjerkovic, D W Scott
Oct 13, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·M NakanishiM Sasaki
Nov 28, 2001·The Plant Journal : for Cell and Molecular Biology·M B Boniotti, C Gutierrez
Jun 24, 2000·European Journal of Biochemistry·P Kaldis, M J Solomon
Sep 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Peter JungHeiko Hermeking
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·S JinnoH Okayama
Dec 12, 2001·Molecular Biology of the Cell·P KaldisM J Solomon
Sep 3, 1998·Molecular Biology of the Cell·P KaldisM J Solomon
Apr 13, 2007·Molecular Biology of the Cell·Christian KannemeierPeiqing Sun
Apr 12, 2013·Molecular Biology of the Cell·Keren TazatYoav I Henis
Jun 22, 2000·Annals of Surgery·D M SimeoneC D Logsdon

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.