加拿大蒙特利爾大學(xué)和舍布魯克大學(xué)的科學(xué)家發(fā)現(xiàn)了一種全新的預(yù)防癌癥的分子機制。該研究詳細(xì)解釋了SOCS1分子是如何防止慢性炎癥性疾病患者的大量致癌細(xì)胞因子的分子機制,，發(fā)表在12月11日的Molecular Cell的雜志上,。
據(jù)研究人員Dr. Gerardo Ferbeyre介紹，機體內(nèi)細(xì)胞因子過多將增加癌癥的發(fā)生。這項研究發(fā)現(xiàn)將有助于科學(xué)家針對那些患慢性炎癥性疾病的病人開發(fā)出預(yù)防癌癥的新方法,，并有助于科學(xué)家更好地了解人類機體對抗癌癥的天然防線,。
課題組發(fā)現(xiàn)，SOCS1是p53基因的直接調(diào)節(jié)因子,，當(dāng)缺失SOCS1時,，p53通路也會受到嚴(yán)重的影響，而人類許多癌癥的發(fā)生就是因為p53基因丟失引起的,。
這項新的研究表明,，患者SOCS1缺失或許也會導(dǎo)致p53腫瘤抑制通路受阻；而將SOCS1分子導(dǎo)入到腫瘤細(xì)胞中,，將會使腫瘤細(xì)胞處于永久休眠狀態(tài)中,，從而抑制癌細(xì)胞的無限增殖。（生物谷Bioon.com）
p53相關(guān)：
Nature Reviews Cancer：抑癌基因p53控制細(xì)胞基因開關(guān)機制
NSMB：抑癌基因p53活性調(diào)控機制
JBC：發(fā)現(xiàn)p53致癌機制
Cancer Cell綜述：miRNA與p53的關(guān)系
AJHG：東亞人群p53基因多態(tài)性的適應(yīng)機制
P53信號通路圖
p53價格/報價搜索結(jié)果-抗體庫-生物在線Lab-on-Web
生物谷推薦原始出處：
Molecular Cell, Volume 36, Issue 5, 754-767, 11 December 2009 doi:10.1016/j.molcel.2009.09.044
SOCS1 Links Cytokine Signaling to p53 and Senescence
Viviane Calabrese1, 3, Frédérick A. Mallette1, 3, 4, Xavier Deschênes-Simard1, Sheela Ramanathan2, Julien Gagnon2, Adrian Moores1, Subburaj Ilangumaran2, , and Gerardo Ferbeyre1, ,
1 Département de Biochimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada
2 Immunology Division, Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada
SOCS1 is lost in many human tumors, but its tumor suppression activities are not well understood. We report that SOCS1 is required for transcriptional activity, DNA binding, and serine 15 phosphorylation of p53 in the context of STAT5 signaling. In agreement, inactivation of SOCS1 disabled p53-dependent senescence in response to oncogenic STAT5A and radiation-induced apoptosis in T cells. In addition, SOCS1 was sufficient to induce p53-dependent senescence in fibroblasts. The mechanism of activation of p53 by SOCS1 involved a direct interaction between the SH2 domain of SOCS1 and the N-terminal transactivation domain of p53, while the C-terminal domain of SOCS1 containing the SOCS Box mediated interaction with the DNA damage-regulated kinases ATM/ATR. Also, SOCS1 colocalized with ATM at DNA damage foci induced by oncogenic STAT5A. Collectively, these results add another component to the p53 and DNA damage networks and reveal a mechanism by which SOCS1 functions as a tumor suppressor.
