QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 13 July 2004
doi: 10.1242/jcs.01210

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.01210v1 117/17/3769    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Naderi, S. Articles by Blomhoff, H. K. Search for Related Content PubMed PubMed Citation Articles by Naderi, S. Articles by Blomhoff, H. K. Social Bookmarking                         What's this?

cAMP-induced degradation of cyclin D3 through association with GSK-3ß

Soheil Naderi^1,*, Kristine B. Gutzkow^1,*, Hege U. Låhne¹, Siri Lefdal¹, W. Johnathan Ryves², Adrian J. Harwood² and Heidi K. Blomhoff^1,

¹ Department of Medical Biochemistry, University of Oslo, P.O. Box 1112 Blindern, Oslo, N-0317, Norway
² MRC Laboratory for Molecular Cell Biology and Department of Biology, University College London, Gower Street, London, WC1E 6BT, UK

Author for correspondence (e-mail: h.k.blomhoff{at}basalmed.uio.no)

Accepted 9 March 2004

In this study we report a new mechanism whereby cyclic AMP (cAMP) regulates the cell-cycle machinery. We demonstrate that elevation of intracellular levels of cAMP promotes degradation of cyclin D3 in proteasomes, and that this occurs via glycogen synthase kinase-3ß (GSK-3ß)-mediated phosphorylation of cyclin D3 at Thr-283. Elevation of cAMP did not change the subcellular distribution of either cyclin D3 or GSK-3ß. However, cAMP promoted the interaction between cyclin D3 and GSK-3ß both in vitro and in vivo, indicating that GSK-3ß-mediated phosphorylation of cyclin D3 might require the association between the two proteins. These results demonstrate how cAMP enhances degradation of cyclin D3. Furthermore, we provide evidence for a novel mechanism by which GSK-3ß might phosphorylate unprimed substrates in vivo.

Key words: cAMP, Cyclin D3, GSK-3ß, Degradation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				L. M. He, D. J. Sartori, M. Teta, L. M. Opare-Addo, M. M. Rankin, S. Y. Long, J. A. Diehl, and J. A. Kushner Cyclin D2 Protein Stability Is Regulated in Pancreatic {beta}-Cells Mol. Endocrinol., November 1, 2009; 23(11): 1865 - 1875. [Abstract] [Full Text] [PDF]

				J. Jin, G.-L. Wang, X. Shi, G. J. Darlington, and N. A. Timchenko The Age-Associated Decline of Glycogen Synthase Kinase 3{beta} Plays a Critical Role in the Inhibition of Liver Regeneration Mol. Cell. Biol., July 15, 2009; 29(14): 3867 - 3880. [Abstract] [Full Text] [PDF]

				J. L. Larabee, K. DeGiusti, J. L. Regens, and J. D. Ballard Bacillus anthracis Edema Toxin Activates Nuclear Glycogen Synthase Kinase 3{beta} Infect. Immun., November 1, 2008; 76(11): 4895 - 4904. [Abstract] [Full Text] [PDF]

				N. Engedal, T. Gjevik, R. Blomhoff, and H. K. Blomhoff All-trans Retinoic Acid Stimulates IL-2-Mediated Proliferation of Human T Lymphocytes: Early Induction of Cyclin D3. J. Immunol., September 1, 2006; 177(5): 2851 - 2861. [Abstract] [Full Text] [PDF]

				Y. Ma, Q. Feng, D. Sekula, J. A. Diehl, S. J. Freemantle, and E. Dmitrovsky Retinoid Targeting of Different D-Type Cyclins through Distinct Chemopreventive Mechanisms Cancer Res., July 15, 2005; 65(14): 6476 - 6483. [Abstract] [Full Text] [PDF]