TPP1 as a versatile player at the ends of chromosomes

TPP1 as a versatile player at the ends of chromosomes
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TPP1 作为染色体末端的多才多艺的参与者

DOI:
10.1007/s11515-014-1307-1
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发表时间:
2014-06
期刊:
Front. Biol
影响因子:
--
通讯作者:
Junjiu Huang
Junjiu Huang
中科院分区:
其他
文献类型:
--
作者:
Sijie Zhang;Zhenhua Luo;Guang Shi;Dan Liu;Zhou Songyang;Junjiu Huang

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端粒是真核生物线性染色体的末端,是串联的DNA重复序列,并被各种端粒蛋白所覆盖。这些核蛋白复合物保护端粒免受DNA损伤反应(DDR),重组和端对端融合,确保基因组稳定性。人类端粒体/shelterin复合物是研究最多的端粒相关蛋白复合物之一,由六个核心端粒蛋白TRF 1、TRF 2、TIN 2、RAP 1、POT 1和TPP 1组成。TPP 1,也称为肾上腺皮质发育不良蛋白同源物(ACD),是TEBP-β的推定哺乳动物同源物,属于含寡核苷酸结合(OB)折叠的蛋白家族。在TPP 1内已经鉴定了三个功能结构域,N-末端OB折叠、POT 1结合募集结构域(RD)和羧基末端TIN 2相互作用结构域(TID)。TPP 1可以与POT 1和TIN 2相互作用以维持端粒结构,并介导端粒酶募集以延长端粒。这些特征表明TPP 1在端粒的维持中起重要作用。在这里,我们将回顾重要的发现,突出TPP 1的功能意义,重点是它与其他端体成分和端粒酶的相互作用。我们还将讨论疾病治疗的潜在影响。
Telomeres, the ends of linear eukaryotic chromosomes, are tandem DNA repeats and capped by various telomeric proteins. These nucleoprotein complexes protect telomeres from DNA damage response (DDR), recombination, and end-to-end fusions, ensuring genome stability. The human telosome/shelterin complex is one of the best-studied telomere-associated protein complexes, made up of six core telomeric proteins TRF1, TRF2, TIN2, RAP1, POT1, and TPP1. TPP1, also known as adrenocortical dysplasia protein homolog (ACD), is a putative mammalian homolog of TEBP-β and belongs to the oligonucleotide binding (OB)-fold-containing protein family. Three functional domains have been identified within TPP1, the N-terminal OB fold, the POT1 binding recruitment domain (RD), and the carboxyl-terminal TIN2-interacting domain (TID). TPP1 can interact with both POT1 and TIN2 to maintain telomere structure, and mediate telomerase recruitment for telomere elongation. These features have indicated TPP1 play an essential role in telomere maintenance. Here, we will review important findings that highlight the functional significance of TPP1, with a focus on its interaction with other telosome components and the telomerase. We will also discuss potential implications in disease therapies.
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端粒蛋白TPP1的TEL斑块介导端粒酶募集和加工性。
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