A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95.
Using a yeast interaction screen to search for proteins that interact with cyclin D3 in thyroid gland, we identified the cAMP-dependent AKAP95 (protein kinase A-anchoring protein 95). AKAP95 is a scaffolding protein that primarily co-fractionates with the nuclear matrix, whereas a minor fraction associates with chromatin in interphase cells. In co-transfected Chinese-hamster ovary cells, AKAP95 strongly interacted with the three D-type cyclins, but not with CDK4 (cyclin-dependent kinase 4) or with p27kip1. CDK4 displaced the interaction between cyclin D3 and AKAP95, suggesting that AKAP95 could not be the elusive bridging adaptor between D-type cyclins and CDK4 or play a role in the regulation of cyclin D3-CDK4 activity. Interaction between endogenous AKAP95 and cyclin D3 or cyclin D1 was detected in canine thyrocytes, human fibroblasts and NIH-3T3 cells. As both AKAP95 and cyclins D were recently reported to associate with minichromosome maintenance proteins [Eide, Tasken, Carlson, Williams, Jahnsen, Tasken and Collas (2003) J. Biol. Chem. 278, 26750-26756; Gladden and Diehl (2003) J. Biol. Chem. 278, 9754-9760], we hypothesize that the interaction between AKAP95 and D-type cyclins might serve to facilitate the emerging regulatory role of cyclin D-CDK4 in the formation of the prereplication complex at the DNA replication origins.
Arsenijevic
Tatjana
T
Institute of Interdisciplinary Research (IRIBHM), School of Medicine, Free University of Brussels, Campus Erasme, Blg C, route de Lennik 808, B-1070 Brussels, Belgium. tarsenij@ulb.ac.be
Degraef
Chantal
C
Dumont
Jacques E
JE
Roger
Pierre P
PP
Pirson
Isabelle
I
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D056741:Cyclin D; D056743:Cyclin D3; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry; D011518:Proto-Oncogene Proteins; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques
D054758:A Kinase Anchor Proteins; C485099:AKAP8 protein, human; D048868:Adaptor Proteins, Signal Transducing; C534696:CCND3 protein, human; D002352:Carrier Proteins; D056741:Cyclin D; D056743:Cyclin D3; D016213:Cyclins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases