Research for unknown targets of cyclin-dependent kinases

细胞周期蛋白依赖性激酶未知靶点的研究

基本信息

批准号：
10480203
负责人：
TAYA Yoichi
金额：
$ 6.14万
依托单位：
NATIONAL CANCER CENTER RESEARCH INSTITUTE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10480203/
关键词：
p16^<INK4a>Cdk4 Cdk6 cyclin D p34^<SEI-1>RB protein Cdk2 合成レチノイド HPR アポトーシス RBタンパク質 CDK PKCη サイクリンE cdk2 サイクリンD1 RB蛋白質 NPAT

项目摘要

The p16INK4a tumor suppressor inhibits cyclin-dependent kinases (CDK4 and CDK6). Here we report the isolation of a novel gene, SEI-1, whose product (p34^<SEI-1>) appears to antagonize the function of p16^<INK4a>. Addition of p34^<SEI-1> to cyclin D1-CDK4 renders the complex resistant to inhibition by p16^<INK4a>. Expression of SEI-1 is rapidly induced onaddition of serum to quiescent fibroblasts, and ectopic expression of p34^<SEI-1> enables fibroblasts to proliferate even in low serum concentrations. p34^<SEI-1> seems to act as a growth factor sensor and may facilitate the formation and activation of cyclin D-CDK complexes in the face of inhibitory levels of INK4 proteins.The p16INK4a tumor suppressor inhibits cyclin-dependent kinases (CDK4 and CDK6). Here we report the isolation of a novel gene, SEI-1, whose product (p34^<SEI-1>) appears to antagonize the function of p16^<INK4a>. Addition of p34^<SEI-1> to cyclin D1-CDK4 renders the complex resistant to inhibition by p16^<INK4a> a. Expression of SEI-1 is rapidly induced on addition of serum to quiescent fibroblasts, and ectopic expression of p34^<SEI-1> enables fibroblasts to proliferate even in low serum concentrations. p34^<SEI-1> seems to act as a growth factor sensor and may facilitate the formation and activation of cyclin D-CDK complexes in the face of inhibitory levels of INK4 proteins.

P16INK4A肿瘤抑制剂抑制细胞周期蛋白依赖性激酶（CDK4和CDK6）。在这里，我们报告了一种新型基因SEI-1的隔离，其产物（p34^<sei-1>）似乎拮抗p16^<ink4a>的功能。在Cyclin D1-CDK4中添加p34^<SEI-1>使p16^<ink4a>抑制的复合物具有抗性。 Sei-1的表达迅速诱导血清吞噬对静止的成纤维细胞，p34^<SEI-1>的异位表达使成纤维细胞也可以在低血清浓度下增殖。 p34^<sei-1>似乎是一种生长因子传感器，可以促进Cyclin d-CDK复合物在抑制水平的Ink4蛋白下的形成和激活。P16INK4A肿瘤抑制剂抑制细胞周期蛋白依赖性的激酶（CDK4和酶） CDK6）。在这里，我们报告了一种新型基因SEI-1的隔离，其产物（p34^<sei-1>）似乎拮抗p16^<ink4a>的功能。在Cyclin D1-CDK4中添加p34^<SEI-1>使p16^<ink4a> a抑制的复合物具有抗性。在静止成纤维细胞中添加血清时，SEI-1的表达迅速诱导，p34^<SEI-1>的异位表达使成纤维细胞即使在低血清浓度下也可以增殖。 p34^<sei-1>似乎充当生长因子传感器，并可能促进在抑制水平的Ink4蛋白下，细胞周期蛋白D-CDK复合物的形成和激活。