日前，美國(guó)托馬斯杰弗遜大學(xué)生物化學(xué)和分子生物系研究人員發(fā)現(xiàn)一種叫做"Caenorhabditis elegans"(生物醫(yī)藥大辭典 提供翻譯)線蟲(chóng)體內(nèi)單一蛋白質(zhì)水平可以確定它們壽命的長(zhǎng)短,。天生不具備這種抑制蛋白(arrestin)的線蟲(chóng)壽命比正常線蟲(chóng)長(zhǎng)三分之一,，而那些抑制蛋白數(shù)量是正常3倍的線蟲(chóng)則壽命短三分之一,。
研究人員指出,，抑制蛋白與其它幾種蛋白質(zhì)發(fā)生交互作用,，從而調(diào)控壽命長(zhǎng)短,。人體相對(duì)應(yīng)的抑制蛋白是PTEN,，它也是一種腫瘤抑制體,。目前，這項(xiàng)最新研究報(bào)告發(fā)表在《生物化學(xué)》雜志上。
生物化學(xué)和分子生物系教授杰弗里-本諾維克(Jeffrey L. Benovic)博士稱(chēng),，由于蟲(chóng)類(lèi)許多蛋白質(zhì)與人類(lèi)相匹配,，這項(xiàng)發(fā)現(xiàn)對(duì)于人體生物學(xué)和理解癌癥的發(fā)展具有特殊貢獻(xiàn)。盡管人體生物學(xué)更加復(fù)雜,，但這種基因?qū)τ谌祟?lèi)和蟲(chóng)類(lèi)之間的關(guān)聯(lián)性暗示著相同的交互作用也存在于哺乳動(dòng)物,。我們需要更深入地展開(kāi)研究，從而獲得更多的重大發(fā)現(xiàn),。
研究人員使用線蟲(chóng)作為實(shí)驗(yàn)?zāi)Ｐ?，由于線蟲(chóng)提供一種簡(jiǎn)單的系統(tǒng)便于研究與人體生物學(xué)相關(guān)的基因和蛋白質(zhì)，例如：“C. elegans”線蟲(chóng)擁有一個(gè)抑制蛋白基因,，相對(duì)應(yīng)地人類(lèi)就有4個(gè),。蠕蟲(chóng)擁有302個(gè)神經(jīng)細(xì)胞，就相當(dāng)于人體大腦1000億個(gè)腦細(xì)胞,。此外,，這種線蟲(chóng)兩至三周的生命周期對(duì)于觀測(cè)長(zhǎng)壽效應(yīng)更加直觀有效。
本諾維克和這項(xiàng)研究報(bào)告第一作者博士后生艾梅-帕爾米特薩(Aimee Palmitessa)研究了由G蛋白質(zhì)對(duì)受體激活的信息路徑,，這些蛋白質(zhì)對(duì)受體可與所有類(lèi)型的激素,、敏感刺激物(比如：光線、氣味等),、神經(jīng)傳遞素等結(jié)合在一起,，它們將刺激細(xì)胞內(nèi)的梯狀信號(hào)，并控制許多生理進(jìn)程,，這種機(jī)理可用于研制藥物,。
本諾維克說(shuō)：“當(dāng)線蟲(chóng)具備這些蛋白質(zhì)對(duì)受體，它們實(shí)際上就變得更加復(fù)雜,，人類(lèi)大概有800種不同的G蛋白質(zhì)對(duì)受體，而線蟲(chóng)依據(jù)不同的感覺(jué)刺激(不同的神經(jīng)傳遞素和激素)具有大約1800種G蛋白質(zhì)對(duì)受體,。”
最初,，抑制蛋白被發(fā)現(xiàn)于細(xì)胞激活狀態(tài)下的蛋白質(zhì)對(duì)受體，本諾維克說(shuō)：“這種線蟲(chóng)提供了一種非常好的方法用于研究單個(gè)抑制蛋白如何與蛋白質(zhì)受體發(fā)生交互感應(yīng),。”
在這項(xiàng)研究中,，帕爾米特薩刪除了線蟲(chóng)體內(nèi)的單個(gè)抑制蛋白基因，觀測(cè)會(huì)發(fā)生什么狀況,，令她驚奇的是,，這些線蟲(chóng)的壽命顯著延長(zhǎng)。她同時(shí)發(fā)現(xiàn)體內(nèi)攜帶更多抑制蛋白基因的線蟲(chóng)壽命會(huì)較短,。
本諾維克博士稱(chēng),，人類(lèi)抑制蛋白基因和PTEN之間的關(guān)聯(lián)性并不清楚，我們并不知道是否人類(lèi)抑制蛋白基因可以控制PTEN的功能，或者在癌癥發(fā)育階段是否出現(xiàn)任何抑制蛋白基因水平的變化,。未來(lái)更深入的研究有助于我們研制抑制人體癌癥的有效醫(yī)學(xué)措施,。（生物谷Bioon.com）
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生物谷推薦原文出處：
JBC doi: 10.1074/jbc.M110.104612
Arrestin and the Multi-PDZ Domain-containing Protein MPZ-1 Interact with Phosphatase and Tensin Homolog (PTEN) and Regulate Caenorhabditis elegans Longevity
Aimee Palmitessa and Jeffrey L. Benovic1
Arrestins are multifunctional adaptor proteins best known for their role in regulating G protein-coupled receptor signaling. Arrestins also regulate other types of receptors, including the insulin-like growth factor receptor (IGF-1R), although the mechanism by which this occurs is not well understood. In Caenorhabditis elegans, the IGF-1R ortholog DAF-2 regulates dauer formation, stress resistance, metabolism, and lifespan through a conserved signaling cascade. To further elucidate the role of arrestin in IGF-1R signaling, we employed an in vivo approach to investigate the role of ARR-1, the sole arrestin ortholog in C. elegans, on longevity. Here, we report that ARR-1 functions to positively regulate DAF-2 signaling in C. elegans. arr-1 mutant animals exhibit increased longevity and enhanced nuclear localization of DAF-16, an indication of decreased DAF-2 signaling, whereas animals overexpressing ARR-1 have decreased longevity. Genetic and biochemical analysis reveal that ARR-1 functions to regulate DAF-2 signaling via direct interaction with MPZ-1, a multi-PDZ domain-containing protein, via a C-terminal PDZ binding domain in ARR-1. Interestingly, ARR-1 and MPZ-1 are found in a complex with the phosphatase and tensin homolog (PTEN) ortholog DAF-18, which normally serves as a suppressor of DAF-2 signaling, suggesting that these three proteins work together to regulate DAF-2 signaling. Our results suggest that the ARR-1-MPZ-1-DAF-18 complex functions to regulate DAF-2 signaling in vivo and provide insight into a novel mechanism by which arrestin is able to regulate IGF-1R signaling and longevity.
