新加坡的科学家通过识别基因DNA的特殊核苷酸序列确定了肿瘤抑制基因p53控制细胞中基因开或关的机制。
这项发现有助于弥补p53基因研究的缺失部分，因为p53在50%以上的癌症中会经历突变或删除。
据介绍，科学家关于P53基因对敏感原件的精确互作已经研究了20年，虽然已经很好了理解了p53打开基因的机制，但还不是很清楚其是如何关闭或抑制基因的。
SIgN研究小组对“抑制”敏感原件的识别为p53的科研人员提供了一个补充，同样对未来的研究具有决定性作用。
这项研究结果发布在10月份的Nature Reviews Cancer和8月份的Proceedings of the National Academy of Sciences上，使科学家能够确定p53复杂通路中的许多基因，或能发现潜在的新的p53通路。
此外，这项研究同样可以使科学家更好地理解p53变异的细胞通路，也可能有助于发现通路中新的癌症靶标区域。
该核苷酸的特定区域，即敏感原件，是很难破译的，这是由于它们有超过100万种可能的组合。所以这项发现确实是很让人兴奋的，研究人员希望这项发现能够对未来的生物医学研究具有积极重要的影响。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
