A novel, extraneuronal role for cyclin-dependent protein kinase 5 (CDK5): modulation of cAMP-induced apoptosis in rat leukemia cells

The Journal of Biological Chemistry
Tone SandalS O Døskeland

Abstract

A number of cyclin-dependent protein kinase (CDK) inhibitors were tested for the ability to protect IPC-81 rat leukemic cells against cAMP-induced apoptosis. A near perfect proportionality was observed between inhibitor potency to protect against cAMP-induced apoptosis and to antagonize CDK5, and to a lesser extent, CDK2 and CDK1. Enforced expression of dominant negative CDK5 (but not CDK1-dn or CDK2-dn) protected against death, indicating that CDK5 activity was necessary for cAMP-induced apoptosis. The CDK inhibitors failed to protect the cells against daunorubicine-, staurosporine-, or okadaic acid-induced apoptosis. The inhibition of CDK5 prevented the cleavage of pro-caspase-3 in cAMP-treated cells. The cells could be saved closer to the moment of their onset of death by inhibitors of caspases than by inhibitors of CDK5. This suggested that the action of CDK5 was upstream of caspase activation. The cAMP treatment resulted in a moderate increase of the level of CDK5 mRNA and protein in IPC-81 wild-type cells. Such cAMP induction of CDK5 was not observed in cells expressing the inducible cAMP early repressor. The cAMP-induced increase of CDK5 contributed to apoptosis since cells overexpressing CDK5-wt were more sensitive for ...Continue Reading

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M R HellmichJ F Battey
Jun 1, 1995·Journal of Cellular Biochemistry·Z Darzynkiewicz
Jun 1, 1995·Journal of Cellular Biochemistry·W Meikrantz, R Schlegel
Sep 1, 1994·European Journal of Biochemistry·J VeselýS Leclerc
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·W MeikrantzR Schlegel
Dec 24, 1993·Science·S van den Heuvel, E Harlow
Apr 26, 1996·The Journal of Biological Chemistry·W Meikrantz, R Schlegel
Mar 19, 1996·Proceedings of the National Academy of Sciences of the United States of America·D L Vaux, A Strasser
Jan 1, 1996·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·D TangJ H Wang
Apr 1, 1997·The International Journal of Biochemistry & Cell Biology·M Arellano, S Moreno
Jan 1, 1995·Progress in Cell Cycle Research·L Meijer
May 23, 1998·Annual Review of Immunology·D T Chao, S J Korsmeyer
May 23, 1998·The International Journal of Biochemistry & Cell Biology·P Sassone-Corsi
Mar 17, 1999·The Journal of Experimental Medicine·A HakemJ M Penninger
May 1, 1999·Reproduction, Nutrition, Development·T Motyl
Jul 10, 1999·The Journal of Biological Chemistry·B B Wolf, D R Green
Dec 1, 1999·Cell Death and Differentiation·D W Nicholson
Jan 12, 2000·The Journal of Cell Biology·K J HarveyD S Ucker
Mar 31, 2000·Experimental Cell Research·H Walczak, P H Krammer
Apr 5, 2000·The Journal of Biological Chemistry·G KusakawaS Hisanaga
May 17, 2000·Pharmaceutica acta Helvetiae·P Schneider, J Tschopp
Aug 10, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·J B LorensG P Nolan
Aug 24, 2000·International Journal of Cancer. Journal International Du Cancer·P ChadebechA Valette
Aug 31, 2000·Annual Review of Biochemistry·A StrasserV M Dixit

❮ Previous
Next ❯

Citations

Jan 10, 2008·Cellular and Molecular Neurobiology·Fatema A Dhariwala, Medha S Rajadhyaksha
Jun 1, 2005·Cancer Letters·Eun-Kyoung YimJong-Sup Park
Jul 16, 2005·Cell Death and Differentiation·L LinZ Zakeri
May 20, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ren LiuZixu Mao
Sep 10, 2010·The Journal of Biological Chemistry·Johanna LieblStefan Zahler
Aug 20, 2003·Molecular Biology of the Cell·Tone SandalStein O Døskeland
Oct 1, 2009·Evidence-based Complementary and Alternative Medicine : ECAM·You-Cheng HseuSheng-Yang Wang
Jan 25, 2011·Journal of Biochemistry·Iva UgrinovaEvdokia A Pasheva
Oct 16, 2009·Journal of Biomedicine & Biotechnology·Yixia YeZahra Zakeri
Jun 14, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·You-Cheng HseuHsin-Ling Yang
Jul 13, 2005·Cellular Microbiology·Daniel E VothJimmy D Ballard
Aug 26, 2004·Cancer Letters·Kwang-Hoon ChunSeung-Ki Lee
May 12, 2004·Neuroscience Letters·Zelda H Cheung, Nancy Y Ip
Apr 29, 2015·Environmental Science and Pollution Research International·Shikha GuptaKunwar P Singh
Nov 13, 2002·The Journal of Biological Chemistry·Adele AffaitatiAntonio Feliciello
Sep 26, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jesusa L Rosales, Ki-Young Lee
May 14, 2010·American Journal of Physiology. Cell Physiology·Mei-Chih ChenPaulus S Wang
Nov 9, 2019·Biomedicines·Rabih Roufayel, Nimer Murshid
Apr 12, 2003·Leukemia & Lymphoma·George P Studzinski, Jonathan S Harrison
Oct 19, 2004·The Journal of Biological Chemistry·Zhen LiNancy Y Ip
Dec 6, 2006·The Journal of Biological Chemistry·Ho LinShih-Yi Lin
Oct 24, 2020·Animals : an Open Access Journal From MDPI·Marta Serna-GarcíaMaría Antonia Santacreu
Jan 23, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Longlong CaoJie Zhang
Dec 29, 2010·Archives of Biochemistry and Biophysics·Hiromi ShimomuraTomoko Nashida
Jun 18, 2003·Accounts of Chemical Research·Laurent Meijer, Eric Raymond
Jun 27, 2007·Journal of Cell Science·Jong-Hee LeeKyong-Tai Kim

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

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.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis