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细胞周期蛋白D依赖性激酶抑制剂Ink4d的胚胎表达与功能

Embryonic Expression and Function of the Ink4d Cyclin D-Dependent Kinase Inhibitor.

作者信息

Doherty Joanne R, Nilsson Lisa M, Kuliyev Emin, Zhu Haiqing, Matthew Rose, Cleveland John L, Mead Paul E, Roussel Martine F

机构信息

Department of Pathology, St. Jude Children's Research Hospital, TN, USA.

Department of Biochemistry St. Jude Children's Research Hospital, TN, USA.

出版信息

Cell Dev Biol. 2014 Feb 15;3(1). doi: 10.4172/2168-9296.1000133.

DOI:10.4172/2168-9296.1000133
PMID:25309971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4192657/
Abstract

Here we report the cloning and functional characterization of the cyclin D-dependent kinase 4 and 6 (Cdk4/6) inhibitory protein Cdkn2d/p19 of (-Ink4d). - is the only family gene highly expressed during development and its transcripts were detected maternally and during neurulation. The -Ink4d protein has 63% identity to mouse and human Cdkn2d/p19 and its function as a negative regulator of cell cycle traverse is evolutionary conserved. Indeed, -lnk4d can functionally substitute for mouse Cdkn2d in binding to mouse Cdk4 and inhibiting cyclin-D1-dependent CDK4 kinase activity. Further, enforced expression of -lnk4d arrests mouse fibroblasts in the G1 phase of the cell cycle. These findings indicate that CDKN2d/p19 is conserved through vertebrate evolution and suggest -lnk4d may contribute to the development of .

摘要

在此,我们报告细胞周期蛋白D依赖性激酶4和6(Cdk4/6)抑制蛋白Cdkn2d/p19(-Ink4d)的克隆及功能特性。-是在发育过程中高度表达的唯一家族基因,其转录本在母体及神经胚形成过程中均可检测到。-Ink4d蛋白与小鼠和人类Cdkn2d/p19具有63%的同源性,其作为细胞周期进程负调控因子的功能在进化上是保守的。实际上,-lnk4d在结合小鼠Cdk4并抑制细胞周期蛋白D1依赖性CDK4激酶活性方面可在功能上替代小鼠Cdkn2d。此外,-lnk4d的强制表达使小鼠成纤维细胞停滞在细胞周期的G1期。这些发现表明CDKN2d/p19在脊椎动物进化过程中是保守的,并提示-lnk4d可能有助于[此处原文缺失具体内容]的发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/4192657/76cf9d1c1f32/nihms582329f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/4192657/c2deb4494fd8/nihms582329f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/4192657/2e983b23e707/nihms582329f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/4192657/76cf9d1c1f32/nihms582329f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/4192657/c2deb4494fd8/nihms582329f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/4192657/2e983b23e707/nihms582329f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc60/4192657/76cf9d1c1f32/nihms582329f3.jpg

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The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation.肿瘤抑制因子Ink4c和p53分别与Patched协同作用,抑制髓母细胞瘤的形成。
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在缺乏早期G1期抑制剂p18INK4C的情况下,造血干细胞的体内自我更新分裂会增加。
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Cranial neural crest-derived mesenchymal proliferation is regulated by Msx1-mediated p19(INK4d) expression during odontogenesis.在牙齿发生过程中,颅神经嵴来源的间充质增殖受Msx1介导的p19(INK4d)表达调控。
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