p53腫瘤抑制因子是一種具有很多生長抑制目標的眾所周知的轉錄激活因子,。p53功能的破壞在多數(shù)癌癥的發(fā)展過程中是一個根本性事件,。微RNA（miRNA）已成為腫瘤抑制中的重要因子，在這項研究工作中，p53 和miRNA之間一個出乎意料的聯(lián)系被發(fā)現(xiàn),。
在一個獨立于它在調(diào)控轉錄中所扮演角色的相互作用中,，作為對DNA損傷的反應，p53增強幾種生長抑制性miRNA的轉錄后成熟過程,，其中包括miR-16-1,、miR-143和miR-145。這表明,，p53調(diào)控miRNA生物生成的能力可能會有助于提高其致癌潛力,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 460, 529-533 (23 July 2009) | doi:10.1038/nature08199
Modulation of microRNA processing by p53
Hiroshi I. Suzuki1, Kaoru Yamagata2,3, Koichi Sugimoto4, Takashi Iwamoto5, Shigeaki Kato2,3 & Kohei Miyazono1
1 Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
2 Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
3 ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchisi, Saitama 332-0012, Japan
4 Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
5 The Center for Education in Laboratory Animal Research and Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan
6 Correspondence to: Kohei Miyazono1 Correspondence and requests for materials should be addressed to K.M.
MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, involved in diverse physiological and pathological processes. Although miRNAs can function as both tumour suppressors and oncogenes in tumour development1, a widespread downregulation of miRNAs is commonly observed in human cancers and promotes cellular transformation and tumorigenesis2, 3, 4. This indicates an inherent significance of small RNAs in tumour suppression. However, the connection between tumour suppressor networks and miRNA biogenesis machineries has not been investigated in depth. Here we show that a central tumour suppressor, p53, enhances the post-transcriptional maturation of several miRNAs with growth-suppressive function, including miR-16-1, miR-143 and miR-145, in response to DNA damage. In HCT116 cells and human diploid fibroblasts, p53 interacts with the Drosha processing complex through the association with DEAD-box RNA helicase p68 (also known as DDX5) and facilitates the processing of primary miRNAs to precursor miRNAs. We also found that transcriptionally inactive p53 mutants interfere with a functional assembly between Drosha complex and p68, leading to attenuation of miRNA processing activity. These findings suggest that transcription-independent modulation of miRNA biogenesis is intrinsically embedded in a tumour suppressive program governed by p53. Our study reveals a previously unrecognized function of p53 in miRNA processing, which may underlie key aspects of cancer biology.
