Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells
Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells
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DOI：
10.1038/sj.onc.1210651
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发表时间：
2008-01-10
期刊：
影响因子：
8
通讯作者：
Chang, M-C
中科院分区：
文献类型：
--
作者：
Chang, T-W;Chen, C-C;Chang, M-C
核糖体酸性 P0 蛋白是真核核糖体茎的重要组成部分，被发现与螺旋-环-螺旋蛋白人 Grap2 和细胞周期蛋白 D 相互作用蛋白 (GCIP)/D 型细胞周期蛋白相互作用蛋白 1/人 MAID 蛋白同源物相互作用。通过体内和体外结合测定，我们表明 P0 可以通过其 N 端 39-114 个氨基酸残基与 GCIP 的 N 和 C 端相互作用。尽管 P0-GCIP 复合物主要在细胞质部分中检测到，但多核糖体 pro.分析表明，P0-GCIP 复合物不与多核糖体或 60S 核糖体共洗脱，表明 GCIP 与细胞质中游离形式的 P0 结合。将 GCIP 转染至 MCF-7 细胞会导致 pRb 磷酸化水平降低。然而，P0 与 GCIP 的共转染导致 GCIP 介导的 pRb 磷酸化水平降低，而 pRb 磷酸化水平被 P0 抑制。此外，与对照转染子相比，乳腺癌和肝细胞癌细胞系中 P0 的过度表达促进了细胞生长和集落形成。 P0 的过表达还增加了细胞周期蛋白 D1 的表达和 pRb Ser780 的磷酸化。有趣的是，P0 mRNA 在 20 对乳腺癌/正常乳腺样本中的 12 对中过度表达（60%）。总之，这些数据表明 P0 过度表达可能至少部分通过抑制 GCIP 介导的肿瘤抑制而导致乳腺和肝脏组织中的肿瘤发生。
The ribosomal acidic P0 protein, an essential component of the eukaryotic ribosomal stalk, was found to interact with the helix-loop-helix protein human Grap2 and cyclin D interacting protein (GCIP)/D-type cyclin-interacting protein 1/human homolog of MAID protein. Using in vivo and in vitro binding assays, we show that P0 can interact with the N and C termini of GCIP via its N-terminal 39-114 amino-acid residues. Although the P0-GCIP complex was detected mainly in cytoplasmic fraction, polysome pro. le analysis indicated that the P0-GCIP complex did not coelute with either polysomes or 60S ribosomes, suggesting that GCIP associates with the free form of P0 in the cytoplasm. Transfection of GCIP into MCF-7 cells resulted in decreased levels of pRb phosphorylation. Cotransfection of P0 with GCIP, however, resulted in GCIP-mediated reduction of pRb phosphorylation level which was repressed by P0. Furthermore, overexpression of P0 in breast cancer and hepatocellular cancer cell lines promoted cell growth and colony formation compared to control transfectants. Overexpression of P0 also increased cyclin D1 expression and phosphorylation of pRb at Ser780. Interestingly, P0 mRNA was overexpressed in 12 of 20 pairs of breast cancer/ normal breast specimens (60%). Together, these data indicate that P0 overexpression may cause tumorigenesis in breast and liver tissues at least in part by inhibiting GCIP-mediated tumor suppression.