加拿大科學(xué)家破解了癌癥發(fā)展過程中一對“至親”蛋白質(zhì)異性體的作用,，相關(guān)論文發(fā)表在《基因與發(fā)育》（Genes and Development）雜志網(wǎng)絡(luò)版上。研究主要負(fù)責(zé)人,，加拿大瑪格麗特王子醫(yī)院坎貝爾家族乳腺癌研究中心的塔克?馬克博士認(rèn)為,，此項(xiàng)發(fā)現(xiàn)為科學(xué)探索開辟新的分支播下了希望的種子,。
這對“至親”蛋白質(zhì)異性體是與基因p53家族相關(guān)的蛋白質(zhì),，而p53家族的“族長”對控制癌癥發(fā)展起著主導(dǎo)作用。當(dāng)p53基因出現(xiàn)缺陷時(shí),，它就喪失了管理健康細(xì)胞并阻止癌癥發(fā)展的機(jī)能,。
直到現(xiàn)在，一般理論仍認(rèn)為這對“至親”蛋白質(zhì)異性體（TAp73蛋白質(zhì)異性體）與癌癥無關(guān),，但此項(xiàng)研究結(jié)果卻推翻了之前的理論,，成為人類了解各類癌癥的基點(diǎn)，并為科學(xué)的進(jìn)一步發(fā)展鋪平了道路,。
馬克博士及其團(tuán)隊(duì)對這對蛋白質(zhì)異性體的傳統(tǒng)定位提出了質(zhì)疑,。“之前，科學(xué)家只針對蛋白質(zhì)異性體的有無進(jìn)行研究,，而我們則更關(guān)心它們是如何相互影響的,。事實(shí)上，我們發(fā)現(xiàn)這對蛋白質(zhì)異性體具有‘人格分裂癥’,，當(dāng)我們‘打開’或‘關(guān)掉’其中一個(gè)‘開關(guān)’時(shí),，另一個(gè)就會改變自身的行為，成為癌癥的誘因之一,。”
馬克博士表示,，此次研究的重點(diǎn)在于了解蛋白質(zhì)異性體發(fā)生相對作用時(shí)的比率，下一步則需要破解這一比率如何影響了細(xì)胞的職責(zé)分配,，并最終導(dǎo)致了癌癥的發(fā)生,。（生物谷Bioon.com）
生物谷推薦原始出處：
Genes and Development，DOI: 10.1101/gad.1695308,，Richard Tomasini,，Tak W. Mak
TAp73 knockout shows genomic instability with infertility and tumor suppressor functions
Richard Tomasini, Katsuya Tsuchihara, Margareta Wilhelm, Masashi Fujitani, Alessandro Rufini, Carol C. Cheung,Fatima Khan, Annick Itie-Youten, Andrew Wakeham, Ming-sound Tsao, Juan L. Iovanna, Jeremy Squire, Igor Jurisica,David Kaplan, Gerry Melino, Andrea Jurisicova, and Tak W. Mak
The Trp53 gene family member Trp73 encodes two major groups of protein isoforms, TAp73 and Np73, with opposing pro- and anti-apoptotic functions; consequently, their relative ratio regulates cell fate. However, the precise roles of p73 isoforms in cellular events such as tumor initiation, embryonic development, and cell death remain unclear. To determine which aspects of p73 function are attributable to the TAp73 isoforms, we generated and characterized mice in which exons encoding the TAp73 isoforms were specifically deleted to create a TAp73-deficient (TAp73–/–) mouse. Here we show that mice specifically lacking in TAp73 isoforms develop a phenotype intermediate between the phenotypes ofTrp73–/– and Trp53–/– mice with respect to incidence of spontaneous and carcinogen-induced tumors, infertility, and aging, as well as hippocampal dysgenesis. In addition, cells from TAp73–/– mice exhibit genomic instability associated with enhanced aneuploidy, which may account for the increased incidence of spontaneous tumors observed in these mutants. Hence, TAp73 isoforms exert tumor-suppressive functions and indicate an emerging role for Trp73 in the maintenance of genomic stability.
