PT  - JOURNAL ARTICLE
AU  - Naderi, Soheil
AU  - Gutzkow, Kristine B.
AU  - Låhne, Hege U.
AU  - Lefdal, Siri
AU  - Ryves, W. Johnathan
AU  - Harwood, Adrian J.
AU  - Blomhoff, Heidi K.
TI  - cAMP-induced degradation of cyclin D3 through association with GSK-3β
AID  - 10.1242/jcs.01210
DP  - 2004 Aug 01
TA  - Journal of Cell Science
PG  - 3769--3783
VI  - 117
IP  - 17
4099  - http://jcs.biologists.org/content/117/17/3769.short
4100  - http://jcs.biologists.org/content/117/17/3769.full
SO  - J. Cell Sci.2004 Aug 01; 117
AB  - 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-3β (GSK-3β)-mediated phosphorylation of cyclin D3 at Thr-283. Elevation of cAMP did not change the subcellular distribution of either cyclin D3 or GSK-3β. However, cAMP promoted the interaction between cyclin D3 and GSK-3β both in vitro and in vivo, indicating that GSK-3β-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-3β might phosphorylate unprimed substrates in vivo.