A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95
A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95
复制标题
DOI：
10.1042/bj20031765
复制
发表时间：
2004-03-01
影响因子：
4.1
通讯作者：
Pirson, I
中科院分区：
文献类型：
--
作者：
Arsenijevic, T;Degraef, C;Pirson, I
使用酵母相互作用筛选来寻找与甲状腺中的细胞周期蛋白03相互作用的蛋白质，我们鉴定了cAMP依赖性AKAP 95（蛋白激酶A锚定蛋白95）。AKAP 95是一种支架蛋白，主要与核基质共分馏，而一小部分与间期细胞中的染色质相关。在共转染的中国仓鼠卵巢细胞中，AKAP 95与三种D型细胞周期蛋白强烈相互作用，但不与CDK 4（细胞周期蛋白依赖性激酶4）或p27（kipl）相互作用。CDK 4取代了cyclin D3和AKAP 95之间的相互作用，这表明AKAP 95可能不是D型cyclin和CDK 4之间难以捉摸的桥接接头，也可能在cyclin D3-CDK 4活性的调节中起作用。在犬甲状腺细胞、人成纤维细胞和NIH-3 T3细胞中检测到内源性AKAP 95与细胞周期蛋白D3或细胞周期蛋白D1之间的相互作用。由于最近报道AKAP 95和细胞周期蛋白D都与微型染色体维持蛋白相关[艾德，Tasken，Carlson，威廉姆斯，Jahnsen，Tasken和Collas（2003）J.Biol.Chem.278，26750-26756; Gladden和Diehl（2003）J.Biol.Chem.278，9754-9760]，我们推测AKAP 95和D型细胞周期蛋白之间的相互作用可能有助于促进细胞周期蛋白D的调节作用。CDK 4在DNA复制起点形成复制前复合物中的作用。
Using a yeast interaction screen to search for proteins that interact with cyclin 03 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 p27(kipl). 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 pre-replication complex at the DNA replication origins.