来自贝勒医学院生物化学与分子生物学系的研究人员发现并证明了人端粒结合因子TRF2如何在不同信号途径中完成调控作用的机制，这对于进一步了解端粒作用，以及端粒和不同信号途径之间的关系具有重要的意义。这一研究成果公布在Nature子刊Nature Structural & Molecular Biology杂志上。
哺乳动物细胞中，端粒结合因子（telomere repeat binding factor,TRF)在端粒酶阳性和阴性细胞中的定位以及在细胞周期中的表达中扮演着重要的角色。其中端粒DNA结合蛋白TRF2(TTAGGG repeat binding factor-2)以二聚体形式通过Myb结构域与端粒重复序列TTAGGG结合，并与TRF1、TIN2、Rap1、TINT1及POT1蛋白组成Shelterin蛋白复合物，协同在端粒动态平衡维持过程中起关键作用，进而影响整个基因组的稳定性。此外，TRF2在细胞DNA损伤应答过程中可能发挥重要作用。
但是迄今为止，科学家们还不了解TRF2与不同信号途径相互作用的机制，在这篇文章中，研究人员利用定向多肽文库，证明人类TRF2的TRFH（TRF同源异形)结构域能识别[Y/F]XL多肽（YYHKYRLSPL），干扰TRF2 TRFH结构域与靶标之间的相互作用还会导致端粒DNA损伤修复。这些研究结果都说明TRF2分子能作为一种蛋白中心，通过聚集不同的信号分子调控端粒。（生物谷Bioon.com）
Nature：研究揭示端粒酶关键部位三维结构
Nature：端粒复合体TBPb的人类同源结构被发现
生物谷推荐原始出处：
Nature Structural & Molecular Biology 16, 372 - 379 (2009) 15 March 2009 | doi:10.1038/nsmb.1575
TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs
Hyeung Kim1,3, Ok-Hee Lee1,3, Huawei Xin1,3, Liuh-Yow Chen1, Jun Qin1, Heekyung Kate Chae1, Shiaw-Yih Lin2, Amin Safari1, Dan Liu1 & Zhou Songyang1
In mammalian cells, the telomeric repeat binding factor (TRF) homology (TRFH) domain–containing telomeric proteins TRF1 and TRF2 associate with a collection of molecules necessary for telomere maintenance and cell-cycle progression. However, the specificity and the mechanisms by which TRF2 communicates with different signaling pathways remain largely unknown. Using oriented peptide libraries, we demonstrate that the TRFH domain of human TRF2 recognizes [Y/F]XL peptides with the consensus motif YYHKYRLSPL. Disrupting the interactions between the TRF2 TRFH domain and its targets resulted in telomeric DNA-damage responses. Furthermore, our genome-wide target analysis revealed phosphatase nuclear targeting subunit (PNUTS) and microcephalin 1 (MCPH1) as previously unreported telomere-associated proteins that directly interact with TRF2 via the [Y/F]XL motif. PNUTS and MCPH1 can regulate telomere length and the telomeric DNA-damage response, respectively. Our findings indicate that an array of TRF2 molecules functions as a protein hub and regulates telomeres by recruiting different signaling molecules via a linear sequence code.
1 Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
2 Department of System Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77054, USA.
3 These authors contributed equally to this work.
