텔로미어 단백질 1의 보호 는 인간에서 POT1 유전자 에 의해 암호화된 단백질 이다.[5] [6] [7] null
함수 이 유전자는 텔롬빈 계열의 일원으로 텔로미어 유지에 관여하는 핵단백질을 암호로 한다. 구체적으로, 이 단백질은 텔로미어의 TTAGGG 반복에 결합되어, 텔로미어의 길이를 조절하고 염색체의 끝을 불법 재결합, 치명적인 염색체 불안정, 비정상적인 염색체 분리로부터 보호하는, 수용체 라고 알려진 다단백질 복합체의 구성원으로서 기능한다. 대안으로 분할된 대본 변형이 설명되었다.[7] null
생쥐 배아 섬유로블라스트와 닭 세포에 POT1이 없으면 텔로미어의 유해한 DNA 손상 반응으로 이어져 말단소성 기능장애 유발 초점(TIFs). 말단소성 방지에 POT1이 필요한 이유는 말단소성 손상 반응 인자의 말단소성 억제가 가능하기 때문이다. 단백질은 또한 말단소립자에 대한 말단소립자 활성을 조절하는 역할도 한다. 인간 POT1을 활용한 시험관내 실험에서 POT1 수치의 감소는 텔로미어의 연장을 초래한다는 것을 보여주었다.[8] null
상호작용 POT1은 ACD [9] [10] [11] TINF2 와 상호작용 하는 것으로 나타났다.[10] [11] [12] null
병리학 참조 ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000128513 - 앙상블 , 2017년 5월^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000029676 - 앙상블 , 2017년 5월^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Baumann P, Cech TR (May 2001). "Pot1, the putative telomere end-binding protein in fission yeast and humans" . Science . 292 (5519): 1171–5. doi :10.1126/science.1060036 . PMID 11349150 . S2CID 11248384 . ^ Baumann P, Podell E, Cech TR (November 2002). "Human Pot1 (protection of telomeres) protein: cytolocalization, gene structure, and alternative splicing" . Molecular and Cellular Biology . 22 (22): 8079–87. doi :10.1128/MCB.22.22.8079-8087.2002 . PMC 134737 PMID 12391173 . ^ a b "Entrez Gene: POT1 POT1 protection of telomeres 1 homolog (S. pombe)" .^ Bauman P, Carolyn P (2010). "Pot1 and telomere maintenance" . FEBS Letters . 584 (17): 3779–3784. doi :10.1016/j.febslet.2010.05.024 . PMC 2942089 PMID 20493859 . ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . 437 (7062): 1173–8. doi :10.1038/nature04209 . PMID 16189514 . S2CID 4427026 . ^ a b Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T (July 2004). "POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex" . Genes & Development . 18 (14): 1649–54. doi :10.1101/gad.1215404 . PMC 478187 PMID 15231715 . ^ a b Liu D, Safari A, O'Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (July 2004). "PTOP interacts with POT1 and regulates its localization to telomeres". Nature Cell Biology . 6 (7): 673–80. doi :10.1038/ncb1142 . PMID 15181449 . S2CID 11543383 . ^ Loayza D, De Lange T (June 2003). "POT1 as a terminal transducer of TRF1 telomere length control". Nature . 423 (6943): 1013–8. doi :10.1038/nature01688 . PMID 12768206 . S2CID 4370276 . ^ Ramsay AJ, Quesada V, Foronda M, Conde L, Martínez-Trillos A, Villamor N, et al. (May 2013). "POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia" . Nature Genetics . 45 (5): 526–30. doi :10.1038/ng.2584 . PMID 23502782 . S2CID 9482133 . ^ Robles-Espinoza CD, Harland M, Ramsay AJ, Aoude LG, Quesada V, Ding Z, et al. (May 2014). "POT1 loss-of-function variants predispose to familial melanoma" . Nature Genetics . 46 (5): 478–481. doi :10.1038/ng.2947 . PMC 4266105 PMID 24686849 . ^ Bainbridge MN, Armstrong GN, Gramatges MM, Bertuch AA, Jhangiani SN, Doddapaneni H, et al. (January 2015). "Germline mutations in shelterin complex genes are associated with familial glioma" . Journal of the National Cancer Institute . 107 (1): 384. doi :10.1093/jnci/dju384 . PMC 4296199 PMID 25482530 .
추가 읽기 de Lange T (September 2005). "Shelterin: the protein complex that shapes and safeguards human telomeres" . Genes & Development . 19 (18): 2100–10. doi :10.1101/gad.1346005 PMID 16166375 . Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery" . Genome Research . 6 (9): 791–806. doi :10.1101/gr.6.9.791 PMID 8889548 . Loayza D, De Lange T (June 2003). "POT1 as a terminal transducer of TRF1 telomere length control". Nature . 423 (6943): 1013–8. doi :10.1038/nature01688 . PMID 12768206 . S2CID 4370276 . Colgin LM, Baran K, Baumann P, Cech TR, Reddel RR (May 2003). "Human POT1 facilitates telomere elongation by telomerase" . Current Biology . 13 (11): 942–6. doi :10.1016/S0960-9822(03)00339-7 PMID 12781132 . S2CID 17801176 . Loayza D, Parsons H, Donigian J, Hoke K, de Lange T (March 2004). "DNA binding features of human POT1: a nonamer 5'-TAGGGTTAG-3' minimal binding site, sequence specificity, and internal binding to multimeric sites" . The Journal of Biological Chemistry . 279 (13): 13241–8. doi :10.1074/jbc.M312309200 PMID 14715659 . Kondo T, Oue N, Yoshida K, Mitani Y, Naka K, Nakayama H, Yasui W (January 2004). "Expression of POT1 is associated with tumor stage and telomere length in gastric carcinoma" . Cancer Research . 64 (2): 523–9. doi :10.1158/0008-5472.CAN-03-1196 PMID 14744765 . Armbruster BN, Linardic CM, Veldman T, Bansal NP, Downie DL, Counter CM (April 2004). "Rescue of an hTERT mutant defective in telomere elongation by fusion with hPot1" . Molecular and Cellular Biology . 24 (8): 3552–61. doi :10.1128/MCB.24.8.3552-3561.2004 . PMC 381596 PMID 15060173 . Liu D, Safari A, O'Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (July 2004). "PTOP interacts with POT1 and regulates its localization to telomeres". Nature Cell Biology . 6 (7): 673–80. doi :10.1038/ncb1142 . PMID 15181449 . S2CID 11543383 . Ye JZ, Hockemeyer D, Krutchinsky AN, Loayza D, Hooper SM, Chait BT, de Lange T (July 2004). "POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex" . Genes & Development . 18 (14): 1649–54. doi :10.1101/gad.1215404 . PMC 478187 PMID 15231715 . Lei M, Podell ER, Cech TR (December 2004). "Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection". Nature Structural & Molecular Biology . 11 (12): 1223–9. doi :10.1038/nsmb867 . PMID 15558049 . S2CID 21018496 . Veldman T, Etheridge KT, Counter CM (December 2004). "Loss of hPot1 function leads to telomere instability and a cut-like phenotype" . Current Biology . 14 (24): 2264–70. doi :10.1016/j.cub.2004.12.031 PMID 15620654 . S2CID 18198999 . Kelleher C, Kurth I, Lingner J (January 2005). "Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro" . Molecular and Cellular Biology . 25 (2): 808–18. doi :10.1128/MCB.25.2.808-818.2005 . PMC 543404 PMID 15632080 . Yang Q, Zheng YL, Harris CC (February 2005). "POT1 and TRF2 cooperate to maintain telomeric integrity" . Molecular and Cellular Biology . 25 (3): 1070–80. doi :10.1128/MCB.25.3.1070-1080.2005 . PMC 544002 PMID 15657433 . Lei M, Zaug AJ, Podell ER, Cech TR (May 2005). "Switching human telomerase on and off with hPOT1 protein in vitro" . The Journal of Biological Chemistry . 280 (21): 20449–56. doi :10.1074/jbc.M502212200 PMID 15792951 . 외부 링크 PDBe-KB 는 말단백질 1(POT1)의 인간 보호를 위해 PDB에서 사용할 수 있는 모든 구조 정보에 대한 개요를 제공한다.
PDB 갤러리
1xjv : 단층 단일 가닥 DNA에 바인딩된 인간 POT1의 결정 구조(TTAGGGGTTAG)
