新加坡的科學(xué)家通過(guò)識(shí)別基因DNA的特殊核苷酸序列確定了腫瘤抑制基因p53控制細(xì)胞中基因開或關(guān)的機(jī)制。

這項(xiàng)發(fā)現(xiàn)有助于彌補(bǔ)p53基因研究的缺失部分,，因?yàn)閜53在50%以上的癌癥中會(huì)經(jīng)歷突變或刪除,。

據(jù)介紹，科學(xué)家關(guān)于P53基因?qū)γ舾性木_互作已經(jīng)研究了20年,，雖然已經(jīng)很好了理解了p53打開基因的機(jī)制,，但還不是很清楚其是如何關(guān)閉或抑制基因的。

SIgN研究小組對(duì)“抑制”敏感原件的識(shí)別為p53的科研人員提供了一個(gè)補(bǔ)充,，同樣對(duì)未來(lái)的研究具有決定性作用,。

這項(xiàng)研究結(jié)果發(fā)布在10月份的Nature Reviews Cancer和8月份的Proceedings of the National Academy of Sciences上，使科學(xué)家能夠確定p53復(fù)雜通路中的許多基因,，或能發(fā)現(xiàn)潛在的新的p53通路,。

此外，這項(xiàng)研究同樣可以使科學(xué)家更好地理解p53變異的細(xì)胞通路,，也可能有助于發(fā)現(xiàn)通路中新的癌癥靶標(biāo)區(qū)域,。

該核苷酸的特定區(qū)域，即敏感原件,，是很難破譯的,，這是由于它們有超過(guò)100萬(wàn)種可能的組合。所以這項(xiàng)發(fā)現(xiàn)確實(shí)是很讓人興奮的,，研究人員希望這項(xiàng)發(fā)現(xiàn)能夠?qū)ξ磥?lái)的生物醫(yī)學(xué)研究具有積極重要的影響,。（生物谷Bioon.com）

生物谷推薦原始出處：

Nature Reviews Cancer 9, 689 (October 2009) | doi:10.1038/nrc2743

Transcription: Reaching a consensus

Nicola McCarthy

p53 regulates gene transcription by binding to a consensus DNA sequence known as a response element (RE). Bei Wang, Ziwei Xiao and Ee Chee Ren have identified core elements in the p53 RE that help to define whether it activates or represses transcription.

PNAS August 25, 2009 vol. 106 no. 34 14373-14378

Redefining the p53 response element

Bei Wanga, Ziwei Xiaob and Ee Chee Rena,b,1

aLaboratory of Immunogenetics, Singapore Immunology Network, A*STAR, 8A Biomedical Grove, 03-06, Immunos, Singapore 138648; and
bDepartment of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, MD4, 5 Science Drive 2, Singapore 119260

The tumor suppressor p53 is a master transcriptional regulator that affects a diverse range of cellular events. Surprisingly, even with >100 validated p53 response element (RE) sequences available, the effect of p53 binding on transcriptional behavior is seldom predictable and no functional rules have been described. Here, we report a systematic study on the role of specific nucleotides within the p53RE by using p21, a well-known target for p53 activation and contrasting it with Lasp1, a gene recently identified to be repressed by p53. Functional assays revealed a specific dinucleotide core combination within the CWWG motif of the p53RE to be the key factor that determines whether p53 transcriptionally activates or represses a target gene. The triplet RRR and YYY sequences flanking the core CWWG motif were also shown to play an important role in modulating the transcriptional behavior of p53. With the establishment of a set of predictive rules, we were able to reassess 162 published p53REs and showed that the attributed function for 20/162 p53REs studied were in fact erroneous. A significant proportion of p53REs (39/162) were found to be repressive, which is substantially higher than what is currently thought. Hence this clearer definition of the transcriptional behavior of p53 interaction with its RE will provide better insight toward the understanding of its fundamental role in cellular networks.