PNUTS (phosphatase nuclear targeting subunit) inhibits retinoblastoma-directed PP1 activity.
PNUTS (phosphatase nuclear targeting subunit) inhibits retinoblastoma-directed PP1 activity.
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PNUTS（磷酸酶核靶向亚基）抑制视网膜母细胞瘤定向的 PP1 活性。
DOI：
10.1016/s0006-291x(02)02236-2
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发表时间：
2002
影响因子：
3.1
通讯作者：
Krucher,NancyA
中科院分区：
文献类型：
--
作者：
Udho,Eshwar;Tedesco,VivienneC;Zygmunt,Adam;Krucher,NancyA
蛋白磷酸酶1型催化亚基（PP 1c）是一种参与真核细胞中许多蛋白质去磷酸化的丝氨酸/苏氨酸磷酸酶。它与几个已知的靶向或调节亚基，直接调节PP 1c对特定底物的活性。最近鉴定的磷酸酶核靶向亚基（PNUTS）与PP 1c结合并抑制PP 1对磷酸化酶a的活性。PP 1c的底物之一已被证明是细胞周期调节蛋白，视网膜母细胞瘤（pRb）。在这项研究中，我们表明，PNUTS从PP 1c在轻度缺氧的细胞生长条件下，导致PP 1c对pRb的活性增加解离。我们开发了一种测定pRb导向的PP 1c活性的方法，并表明当使用来自细胞裂解物、GST-PP 1c或纯化的PP 1c的PP 1c时，GST-PNUTS融合蛋白抑制磷酸酶对pRb的活性。这些研究表明，PNUTS参与调节PP 1c对pRb的活性。
Protein phosphatase type 1 catalytic subunit (PP1c) is a serine/threonine phosphatase involved in the dephosphorylation of many proteins in eukaryotic cells. It associates with several known targeting or regulatory subunits that directly regulate PP1c activity toward specific substrates. The recently identified Phosphatase Nuclear Targeting Subunit (PNUTS) binds to PP1c and inhibits PP1 activity toward phosphorylase a. One of the substrates of PP1c has been shown to be the cell cycle regulatory protein, Retinoblastoma (pRb). In this study, we show that PNUTS dissociates from PP1c under mildly hypoxic cell growth conditions that lead to an increase of PP1c activity toward pRb. We developed an assay that measures pRb-directed PP1c activity and show that a GST-PNUTS fusion protein inhibits phosphatase activity toward pRb when using PP1c from cell lysates, GST-PP1c, or purified PP1c. These studies suggest that PNUTS is involved in the regulation of PP1c activity toward pRb.