Non-CDK-bound p27 (p27{sup NCDK}) is a marker for cell stress and is regulated through the Akt/PKB and AMPK-kinase pathways

Journal Article · Wed Mar 10 00:00:00 EST 2010 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2009.12.014· OSTI ID:22209870

Bjoerklund, Mia A. ^[1]; Vaahtomeri, Kari ^[2]; Peltonen, Karita ^[1]; Viollet, Benoit ^[3]; INSERM U567, 75014 Paris ^[4]; Maekelae, Tomi P. ^[2]; Band, Arja M. ^[1]; Laiho, Marikki ^[1]

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1. Molecular Cancer Biology Program, Biomedicum Helsinki and Haartman Institute, University of Helsinki, Helsinki (Finland)
2. Genome-Scale Biology Program and Institute of Biotechnology, 00014 University of Helsinki, Helsinki (Finland)
3. Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), 75014 Paris (France)
4. France

p27Kip1 (p27) tumour suppressor protein is regulated by multiple mechanisms including its turnover, localization and complex formation with its key targets, cyclin-dependent kinases (CDK) and cyclins. We have earlier shown that p27 exists in cells in a form that lacks cyclin/CDK interactions (hence non-CDK, p27{sup NCDK}) but the nature of p27{sup NCDK} has remained unresolved. Here we demonstrate that the epitope recognized by the p27{sup NCDK}-specific antibody resides in the p27 CDK-interaction domain and that p27{sup NCDK} is regulated by the balance of CDK inhibitors and cyclin-CDK complexes. We find that signalling by cellular growth promoting pathways, like phosphoinositol 3-kinase (PI3K) and specifically Akt/PKB kinase, inversely correlates with p27{sup NCDK} levels whereas total p27 levels are unaffected. p27{sup NCDK}, but not total p27, is increased by cellular perturbations such as hyperosmotic and metabolic stress and activation of AMP-activated protein kinase (AMPK). By using AMPK catalytic subunit proficient and deficient cells we further demonstrate that the AMPK pathway governs p27{sup NCDK} responses to metabolic stress and PI3K inhibition. These results indicate that p27{sup NCDK} is a sensitive marker for both cell stress and proliferation over and above p27 and is regulated by Akt/PKB and AMPK pathways.

• OSTI ID: 22209870
• Journal Information: Experimental Cell Research, Vol. 316, Issue 5; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMP
ANTIBODIES
CELL PROLIFERATION
FIBROBLASTS
GROWTH FACTORS
INHIBITION
PERTURBATION THEORY
PHOSPHOTRANSFERASES