Interaction of CR6 (GADD45γ) with proliferating cell nuclear antigen impedes negative growth control
Interaction of CR6 (GADD45γ) with proliferating cell nuclear antigen impedes negative growth control
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DOI：
10.1074/jbc.m005626200
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发表时间：
2001-01-26
影响因子：
4.8
通讯作者：
Liebermann, DA
中科院分区：
文献类型：
--
作者：
Azam, N;Vairapandi, M;Liebermann, DA
GADD45、MyDII8 和 CR6（也称为 GADD45 α、β 和 γ）包含一个基因家族，这些基因编码在负生长控制（包括生长抑制）中发挥重要作用的相关蛋白。积累的数据表明，MyD118/GADD45/CR6 在不同的细胞凋亡和生长抑制途径中发挥相似但不相同的功能。同样明显的是，MyD118/GADD45/CR6 家族的个体成员受到多种遗传和环境应激因素的差异诱导。 MyD118、CR6 和 GADD45 蛋白主要定位于细胞核内。最近，我们发现 MyD118 和 GADD45 都与增殖细胞核抗原 (PCNA) 相互作用，PCNA 是一种在 DNA 复制、DNA 修复和细胞周期进展中起核心作用的蛋白质，以及通用细胞周期蛋白依赖性激酶抑制剂 p21。在这项工作中，我们表明 CR6 也与 PCNA 和 p21 相互作用。此外，研究表明 CR6 通过一个也介导 GADD45 和 PCNA 相互作用的结构域与 PCNA 相互作用。 MyD118 与 PCNA。重要的是，已有证据表明 CR6 与 PCNA 的相互作用会阻碍该蛋白在负生长控制中的功能，与 MyD118 和 GADD45 的观察结果类似 (1)。
GADD45, MyDII8, and CR6 (also termed GADD45 alpha, beta, and gamma) comprise a family of genes that encode for related proteins playing important roles in negative growth control, including growth suppression. Data accumulated suggest that MyD118/GADD45/CR6 serve similar but not identical functions along different apoptotic and growth suppressive pathways. It is also apparent that individual members of the MyD118/GADD45/CR6 family are differentially induced by a variety of genetic and environmental stress agents. The MyD118, CR6, and GADD45 proteins were shown to predominantly localize within the cell nucleus. Recently, we have shown that both MyD118 and GADD45 interact with proliferating cell nuclear antigen (PCNA), a protein that plays a central role in DNA replication, DNA repair, and cell cycle progression, as well as with the universal cyclin-dependent kinase inhibitor p21, In this work we show that also CR6 interacts with PCNA and p21, Moreover, it is shown that CR6 interacts with PCNA via a domain that also mediates interaction of both GADD45 and MyD118 with PCNA. Importantly, evidence has been obtained that interaction of CR6 with PCNA impedes the function of this protein in negative growth control, similar to observations reported for MyD118 and GADD45 (1).