liu.seSök publikationer i DiVA
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis
Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, R3E 0V9, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, R3E 0V9, Canada.
Manitoba Institute of Cell Biology, CancerCare Manitoba; Department of Human Genetics, University of Aarhus, Aarhus, Denmark; Department of Experimental and Clinical Radiobiology, Oncology Center, Maria Sklodowka-Curie Memorial Institute, Wybrzeze Armii Krajowej 15, PL-44100 Gliwice, Poland .
Department of Experimental and Clinical Radiobiology, Oncology Center, Maria Sklodowka-Curie Memorial Institute, Wybrzeze Armii Krajowej 15, PL-44100 Gliwice, Poland .
Visa övriga samt affilieringar
2008 (Engelska)Ingår i: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 121, s. 979-988Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Here, we show that CDK2, an S-phase cyclin-dependent kinase, is a novel target for Akt during cell cycle progression and apoptosis. Akt phosphorylates CDK2 at threonine 39 residue both in vitro and in vivo. Although CDK2 threonine 39 phosphorylation mediated by Akt enhances cyclin-A binding, it is dispensable for its basal binding and the kinase activity. In addition, for the first time, we report a transient nucleo-cytoplasmic shuttling of Akt during specific stages of the cell cycle, in particular during the late S and G2 phases. The Akt that is re-localized to the nucleus phosphorylates CDK2 and causes the temporary cytoplasmic localization of the CDK2–cyclin-A complex. The CDK2 cytoplasmic redistribution is required for cell progression from S to G2-M phase, because the CDK2 T39A mutant, which lacks the phosphorylation site and is defective in cytoplasmic localization, severely affects cell cycle progression at the transition from S to G2-M. Interestingly, we also show that the Akt/CDK2 pathway is constitutively activated by some anticancer drugs, such as methotrexate and docetaxel, and under these conditions it promotes, rather than represses, cell death. Thus, the constitutive activation of the Akt/CDK2 pathway and changed subcellular localization promotes apoptosis. By contrast, the transient, physiological Akt/CDK2 activation is necessary for cell cycle progression.

Ort, förlag, år, upplaga, sidor
The Company of Biologists Ltd. , 2008. Vol. 121, s. 979-988
Nyckelord [en]
Akt Apoptosis Anti-cancer drugs Cdk2 Cell cycle
Nationell ämneskategori
Cancer och onkologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Cellbiologi Biokemi och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:liu:diva-86929DOI: 10.1242/jcs.009530ISI: 000254660300008PubMedID: 18354084OAI: oai:DiVA.org:liu-86929DiVA, id: diva2:583320
Tillgänglig från: 2013-01-07 Skapad: 2013-01-07 Senast uppdaterad: 2017-12-06

Open Access i DiVA

fulltext(478 kB)489 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 478 kBChecksumma SHA-512
db234496b4f1da793e1411ab40f9c343fc96ba8ec5893688d1cb7bd28b1c20bd34d6a94e2f007f9a9695c266462a2250a06627c1519a53daf34e86a53b49dd52
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Wiechec, EmiliaLos, Marek Jan

Sök vidare i DiVA

Av författaren/redaktören
Wiechec, EmiliaLos, Marek Jan
I samma tidskrift
Journal of Cell Science
Cancer och onkologiMedicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)CellbiologiBiokemi och molekylärbiologi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 489 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 395 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf