Ubiquitylation of ε-COP by PIRH2 and regulation of the secretion of PSA
Ubiquitylation of ε-COP by PIRH2 and regulation of the secretion of PSA
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DOI：
10.1007/s11010-007-9586-3
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发表时间：
2007-08
影响因子：
4.3
通讯作者：
S. Maruyama;N. Miyajima;M. Bohgaki;T. Tsukiyama;Masahiko Shigemura;K. Nonomura;S. Hatakeyama
中科院分区：
文献类型：
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作者：
S. Maruyama;N. Miyajima;M. Bohgaki;T. Tsukiyama;Masahiko Shigemura;K. Nonomura;S. Hatakeyama
泛素化似乎参与了膜运输系统，包括内吞作用、胞吐作用和ER到高尔基体的运输。我们发现PIRH 2是一种与雄激素受体或p53相互作用的蛋白质，它与ε-COP的ε-亚基相互作用并使其泛素化。PIRH 2在体内外均能促进ε-COP的泛素化，从而促进ε-COP的降解。PIRH 2和ε-COP之间的相互作用受到雄激素的影响，并且PIRH 2在雄激素存在下促进体内ε-COP的泛素化。此外，野生型PIRH 2在前列腺癌细胞中的过表达导致前列腺特异性抗原（PSA）的分泌下调，PSA是前列腺上皮细胞中的分泌蛋白，并且是前列腺癌的诊断标志物之一。我们的研究结果表明，PIRH 2作为COP I复合物的调节剂发挥作用。
Ubiquitylation appears to be involved in the membrane trafficking system including endocytosis, exocytosis, and ER-to-Golgi transport. We found that PIRH2, which was identified as an interacting protein for androgen receptor or p53, interacts with and ubiquitylates the ε-subunit of coatmer complex, ε-COP. PIRH2 promotes the ubiquitylation of ε-COP in vitro and in vivo and consequently promotes the degradation of ε-COP. The interaction between PIRH2 and ε-COP is affected by the presence of androgen, and PIRH2 in the presence of androgen promotes ubiquitylation of ε-COP in vivo. Furthermore, overexpression of the wild type of PIRH2 in prostate cancer cells causes downregulation of the secretion of prostate-specific antigen (PSA), a secretory protein in prostate epithelial cells and one of diagnostic markers for prostate cancer. Our results indicate that PIRH2 functions as a regulator for COP I complex.