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, a...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, RAPI, POT1, and TPPI. 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.展开更多
目的检测端粒保护蛋白POT1(protection of telomeres 1)m RNA和TPP1(POT1-interacting protein 1)m RNA在膀胱尿路上皮癌中的表达。分析两者表达的相关性及与膀胱尿路上皮癌的病理分级、临床分期之间的关系。方法收集32例膀胱尿路上皮...目的检测端粒保护蛋白POT1(protection of telomeres 1)m RNA和TPP1(POT1-interacting protein 1)m RNA在膀胱尿路上皮癌中的表达。分析两者表达的相关性及与膀胱尿路上皮癌的病理分级、临床分期之间的关系。方法收集32例膀胱尿路上皮癌组织标本,17例癌旁组织标本,12例正常膀胱粘膜组织标本。提取各组标本的总RNA,采用实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-q PCR)检测端粒保护蛋白POT1 m RNA和TPP1m RNA在各组标本中的表达。结果 POT 1 m RNA、TPP 1 m RNA在膀胱尿路上皮癌组织组中的相对表达量,均低于其在癌旁组织组中的相对表达量,组间差异有统计学意义(P<0.01);且均低于其在正常膀胱粘膜组织组中的相对表达量,组间差异有统计学意义(P<0.01);而POT 1 m RNA、TPP 1 m RNA的相对表达量在癌旁组织组与正常膀胱粘膜组织组相比较,组间差异无统计学意义。在各组标本中,POT 1 m RNA与TPP 1 m RNA相对表达量之间成线性相关。膀胱尿路上皮癌组织中POT1 m RNA、TPP 1 m RNA的相对表达量在各病理分级间差异无统计学意义,而膀胱尿路上皮癌组织中POT1m RNA、TPP 1m RNA的相对表达量在临床分期间的差异有统计学意义,并且随着临床分期的增加而升高。结论端粒保护蛋白POT1 m RNA和TPP1 m RNA在膀胱尿路上皮癌组织中的表达低于癌旁组织及正常粘膜组织。POT1 m RNA和TPP1 m RNA的表达之间线性相关。端粒保护蛋白POT1和TPP1的表达可能与膀胱肿瘤的发生及病理分级、临床分期存在相关性。展开更多
基金Acknowledgements This study was supported by the National Basic Research Program （973 Program） （Nos. 2012CB911201 and 2010CB945401）, the National Natural Science Foundation （Grant Nos. 31371508, 91019020 and 81330055）, the Introduced Innovative R and D Team of Guangdong Province （No. 201001Y0104687244）, Zhujiang Program of Science and Technology Nova in Guangzhou （No. 2011 J2200082）.
文摘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, RAPI, POT1, and TPPI. 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.
文摘目的检测端粒保护蛋白POT1(protection of telomeres 1)m RNA和TPP1(POT1-interacting protein 1)m RNA在膀胱尿路上皮癌中的表达。分析两者表达的相关性及与膀胱尿路上皮癌的病理分级、临床分期之间的关系。方法收集32例膀胱尿路上皮癌组织标本,17例癌旁组织标本,12例正常膀胱粘膜组织标本。提取各组标本的总RNA,采用实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-q PCR)检测端粒保护蛋白POT1 m RNA和TPP1m RNA在各组标本中的表达。结果 POT 1 m RNA、TPP 1 m RNA在膀胱尿路上皮癌组织组中的相对表达量,均低于其在癌旁组织组中的相对表达量,组间差异有统计学意义(P<0.01);且均低于其在正常膀胱粘膜组织组中的相对表达量,组间差异有统计学意义(P<0.01);而POT 1 m RNA、TPP 1 m RNA的相对表达量在癌旁组织组与正常膀胱粘膜组织组相比较,组间差异无统计学意义。在各组标本中,POT 1 m RNA与TPP 1 m RNA相对表达量之间成线性相关。膀胱尿路上皮癌组织中POT1 m RNA、TPP 1 m RNA的相对表达量在各病理分级间差异无统计学意义,而膀胱尿路上皮癌组织中POT1m RNA、TPP 1m RNA的相对表达量在临床分期间的差异有统计学意义,并且随着临床分期的增加而升高。结论端粒保护蛋白POT1 m RNA和TPP1 m RNA在膀胱尿路上皮癌组织中的表达低于癌旁组织及正常粘膜组织。POT1 m RNA和TPP1 m RNA的表达之间线性相关。端粒保护蛋白POT1和TPP1的表达可能与膀胱肿瘤的发生及病理分级、临床分期存在相关性。
