研究揭示了蛋白質(zhì)如何抑制小鼠腫瘤的發(fā)展

研究揭示了蛋白質(zhì)如何抑制小鼠腫瘤的發(fā)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.

蛋白質(zhì)存在于我們的細(xì)胞中，調(diào)節(jié)著許多對(duì)我們生存很重要的生物過(guò)程。但其中一些還調(diào)節(jié)了可能讓我們生病的過(guò)程?，F(xiàn)在，一個(gè)由來(lái)自哥本哈根大學(xué)的研究人員組成的國(guó)際研究小組，已經(jīng)對(duì)其中一種蛋白質(zhì)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.

在一項(xiàng)新的研究中，研究人員發(fā)現(xiàn)了蛋白質(zhì)PP2A在分子水平上是如何工作的，以及它如何抑制小鼠腫瘤的發(fā)展。新的研究結(jié)果已經(jīng)發(fā)表在科學(xué)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."

“我們稱PP2A為家庭蛋白，因?yàn)樗鼛缀鯚o(wú)處不在。在所有生物中——從簡(jiǎn)單的酵母細(xì)胞到人類的復(fù)雜細(xì)胞。PP2A去除其他蛋白質(zhì)上的磷酸基，現(xiàn)在我們已經(jīng)發(fā)現(xiàn)了這些蛋白質(zhì)，以及PP2A是如何通過(guò)其中一種蛋白質(zhì)抑制癌癥發(fā)展的。”

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

諾和諾德基金會(huì)蛋白質(zhì)研究中心教授雅各布·尼爾森說(shuō)。

Turned-off enzyme

關(guān)閉酶

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.

據(jù)研究人員稱，學(xué)術(shù)界和制藥業(yè)都對(duì)PP2A蛋白非常感興趣，因?yàn)楸娝苤琍P2A是一種抑制腫瘤的所謂的腫瘤抑制因子。但究竟是哪些PP2A蛋白質(zhì)調(diào)控，以抑制癌癥至今仍不清楚。現(xiàn)在，研究人員對(duì)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.

“我們研究的新發(fā)現(xiàn)是，我們展示了PP2A如何選擇從其他蛋白質(zhì)中去除的磷酸基。”同時(shí)，我們發(fā)現(xiàn)PP2A會(huì)關(guān)閉一種叫做ADAM17的酶。來(lái)自生物技術(shù)研究與創(chuàng)新中心的副教授瑪麗·科維伯格解釋說(shuō)，這種ADAM17的關(guān)閉抑制了小鼠腫瘤生長(zhǎng)。

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.

研究人員使用先進(jìn)的方法證明，PP2A可以通過(guò)去除位于細(xì)胞內(nèi)部的ADAM17部分的磷酸基團(tuán)，來(lái)關(guān)閉細(xì)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.

正常情況下，ADAM17在細(xì)胞外膜中充當(dāng)分子剪刀，從細(xì)胞表面劈開(kāi)其他蛋白質(zhì)——例如，刺激細(xì)胞生長(zhǎng)的生長(zhǎng)因子。但是當(dāng)PP2A從ADAM17中去除磷酸基時(shí)，這個(gè)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.

研究人員已經(jīng)從之前的研究中得知，ADAM17會(huì)刺激多種癌癥，包括乳腺癌和腸癌。但這是PP2A第一次被證明可以積極地關(guān)閉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.

接下來(lái)，研究人員希望他們的新癌癥發(fā)現(xiàn)也適用于人類腫瘤。目前，研究人員的下一步是弄清楚激活PP2A的物質(zhì)是否可以用來(lái)調(diào)節(jié)ADAM17的活性。此外，研究人員還想研究PP2A如何調(diào)節(jié)其他蛋白質(zhì)，這可能對(duì)了解其腫瘤抑制功能很重要。