研究揭示了蛋白质如何抑制小鼠肿瘤的发展

研究揭示了蛋白质如何抑制小鼠肿瘤的发展

Proteins are found throughout our cells and regulate a lot of biological processes that are important for our survival. But some of them also regulate processes that can make us sick. Now, an international research team, with researchers from the University of Copenhagen at the forefront, has achieved a much better understanding of one such protein.

蛋白质存在于我们的细胞中，调节着许多对我们生存很重要的生物过程。但其中一些还调节了可能让我们生病的过程。现在，一个由来自哥本哈根大学的研究人员组成的国际研究小组，已经对其中一种蛋白质有了更深入的了解。

In a new study, the researchers discovered how the protein PP2A works at the molecular level, and how it inhibits the development of tumors in mice. The new results have been published in the scientific journal, the EMBO Journal.

在一项新的研究中，研究人员发现了蛋白质PP2A在分子水平上是如何工作的，以及它如何抑制小鼠肿瘤的发展。新的研究结果已经发表在科学期刊EMBO期刊上。

“We call PP2A a household protein because it is found almost everywhere. In everything living - from simple yeast cells to complex cells in humans. PP2A removes phosphate groups on other proteins, and now we have found these proteins and how PP2A, via one of these proteins, inhibits cancer development."

“我们称PP2A为家庭蛋白，因为它几乎无处不在。在所有生物中——从简单的酵母细胞到人类的复杂细胞。PP2A去除其他蛋白质上的磷酸基，现在我们已经发现了这些蛋白质，以及PP2A是如何通过其中一种蛋白质抑制癌症发展的。”

Jakob Nilsson, Professor, Novo Nordisk Foundation Center for Protein Research.

诺和诺德基金会蛋白质研究中心教授雅各布·尼尔森说。

Turned-off enzyme

关闭酶

According to the researchers, there is a great deal of interest from both the academic research community and from the pharmaceutical industry for the protein PP2A because it is well-known that PP2A is a so-called tumor suppressor that suppresses tumors. But precisely which proteins PP2A regulates in order to inhibit cancer have so far not been known. Now, the researchers have gained detailed insight into this.

据研究人员称，学术界和制药业都对PP2A蛋白非常感兴趣，因为众所周知，PP2A是一种抑制肿瘤的所谓的肿瘤抑制因子。但究竟是哪些PP2A蛋白质调控，以抑制癌症至今仍不清楚。现在，研究人员对此有了更深入的了解。

'The new thing about our study is that we show how PP2A selects the phosphate groups that shall be removed from other proteins. And then at the same time, we show that PP2A turns off an enzyme named ADAM17. This shutdown of ADAM17 results in inhibition of tumor growth in mice', explains Associate Professor Marie Kveiborg from the Biotech Research and Innovation Centre.

“我们研究的新发现是，我们展示了PP2A如何选择从其他蛋白质中去除的磷酸基。”同时，我们发现PP2A会关闭一种叫做ADAM17的酶。来自生物技术研究与创新中心的副教授玛丽·科维伯格解释说，这种ADAM17的关闭抑制了小鼠肿瘤生长。

The researchers have used advanced methods to show that PP2A can turn off the activity of ADAM17 on the outside of the cell by removing phosphate groups from the part of ADAM17 that is located inside the cell.

研究人员使用先进的方法证明，PP2A可以通过去除位于细胞内部的ADAM17部分的磷酸基团，来关闭细胞外部的ADAM17的活性。

The function is inhibited

功能受到抑制

Normally, ADAM17 sits as a pair of molecular scissors in the cell's outer membrane and cleaves other proteins from the cell surface - for example, growth factors that will then stimulate cell growth. But that function ceases when PP2A removes the phosphate groups from ADAM17.

正常情况下，ADAM17在细胞外膜中充当分子剪刀，从细胞表面劈开其他蛋白质——例如，刺激细胞生长的生长因子。但是当PP2A从ADAM17中去除磷酸基时，这个功能就停止了。

The researchers already knew from previous studies that ADAM17 stimulates a variety of cancers, including breast and bowel cancer. But this is the first time that PP2A has been shown to actively turn off ADAM17 activity.

研究人员已经从之前的研究中得知，ADAM17会刺激多种癌症，包括乳腺癌和肠癌。但这是PP2A第一次被证明可以积极地关闭ADAM17活性。

Going forward, the researchers hope that their new cancer discovery will also apply to human tumors. For now, the next step for the researchers is to clarify whether substances that activate PP2A can be used to regulate ADAM17 activity. In addition, the researchers also want to look at how PP2A regulates other proteins that may be important for the understanding of its tumor suppressor function.

接下来，研究人员希望他们的新癌症发现也适用于人类肿瘤。目前，研究人员的下一步是弄清楚激活PP2A的物质是否可以用来调节ADAM17的活性。此外，研究人员还想研究PP2A如何调节其他蛋白质，这可能对了解其肿瘤抑制功能很重要。