加拿大科学家破解了癌症发展过程中一对“至亲”蛋白质异性体的作用，相关论文发表在《基因与发育》（Genes and Development）杂志网络版上。研究主要负责人，加拿大玛格丽特王子医院坎贝尔家族乳腺癌研究中心的塔克?马克博士认为，此项发现为科学探索开辟新的分支播下了希望的种子。
这对“至亲”蛋白质异性体是与基因p53家族相关的蛋白质，而p53家族的“族长”对控制癌症发展起着主导作用。当p53基因出现缺陷时，它就丧失了管理健康细胞并阻止癌症发展的机能。
直到现在，一般理论仍认为这对“至亲”蛋白质异性体（TAp73蛋白质异性体）与癌症无关，但此项研究结果却推翻了之前的理论，成为人类了解各类癌症的基点，并为科学的进一步发展铺平了道路。
马克博士及其团队对这对蛋白质异性体的传统定位提出了质疑。“之前，科学家只针对蛋白质异性体的有无进行研究，而我们则更关心它们是如何相互影响的。事实上，我们发现这对蛋白质异性体具有‘人格分裂症’，当我们‘打开’或‘关掉’其中一个‘开关’时，另一个就会改变自身的行为，成为癌症的诱因之一。”
马克博士表示，此次研究的重点在于了解蛋白质异性体发生相对作用时的比率，下一步则需要破解这一比率如何影响了细胞的职责分配，并最终导致了癌症的发生。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
