Open AccesscAMP-induced degradation of cyclin D3 through association with GSK-3β
Author(s) -
Soheil Naderi,
Kristine B. Gützkow,
Hege U. Låhne,
Siri Lefdal,
W.J. Ryves,
Adrian J. Harwood,
Heidi Kiil Blomhoff
Publication year - 2004
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.01210
Subject(s) - biology , cyclin dependent kinase complex , cyclin d , cyclin a , gsk 3 , cyclin , cyclin d1 , microbiology and biotechnology , cyclin a2 , phosphorylation , cyclin b , cyclin d3 , cyclin e , biochemistry , cell cycle , protein kinase a , cyclin dependent kinase 2 , cell
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-3beta (GSK-3beta)-mediated phosphorylation of cyclin D3 at Thr-283. Elevation of cAMP did not change the subcellular distribution of either cyclin D3 or GSK-3beta. However, cAMP promoted the interaction between cyclin D3 and GSK-3beta both in vitro and in vivo, indicating that GSK-3beta-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-3beta might phosphorylate unprimed substrates in vivo.
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