Biology:POT1

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A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Protection of telomeres protein 1 is a protein that in humans is encoded by the POT1 gene.[1][2][3]

Function

This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein functions as a member of a multi-protein complex known as shelterin, that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. Alternatively spliced transcript variants have been described.[3]

The absence of POT1 in mouse embryonic fibroblasts and chicken cells leads to a detrimental DNA damage response on telomeres resulting in telomere dysfunction-induced foci (TIFs). POT1 is required for telomere protection because it allows for telomere inhibition of DNA damage response factors. The protein also serves a role in the regulation of telomerase activity on telomeres. In vitro experiments utilizing human POT1 have shown that reduction in POT1 levels result in the elongation of telomeres.[4]

Interactions

POT1 has been shown to interact with ACD[5][6][7] and TINF2.[6][7][8]

Pathology

  • Increased transcriptional expression of this gene is associated with stomach carcinogenesis and its progression.
  • Mutations in this gene have also been associated to the acquisition of the malignant features of chronic lymphocytic leukemia.[9]
  • POT1 loss-of-function variants predispose to familial melanoma[10] and glioma.[11]

References

  1. ↑ "Pot1, the putative telomere end-binding protein in fission yeast and humans". Science 292 (5519): 1171–5. May 2001. doi:10.1126/science.1060036. PMID 11349150. 
  2. ↑ "Human Pot1 (protection of telomeres) protein: cytolocalization, gene structure, and alternative splicing". Molecular and Cellular Biology 22 (22): 8079–87. November 2002. doi:10.1128/MCB.22.22.8079-8087.2002. PMID 12391173. 
  3. ↑ 3.0 3.1 "Entrez Gene: POT1 POT1 protection of telomeres 1 homolog (S. pombe)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=25913. 
  4. ↑ Bauman, Peter; Carolyn, Price (2010). "Pot1 and telomere maintenance". FEBS Letters 584 (17): 3779-3784. doi:10.1016/j.febslet.2010.05.024. 
  5. ↑ "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. 
  6. ↑ 6.0 6.1 "POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex". Genes & Development 18 (14): 1649–54. July 2004. doi:10.1101/gad.1215404. PMID 15231715. 
  7. ↑ 7.0 7.1 "PTOP interacts with POT1 and regulates its localization to telomeres". Nature Cell Biology 6 (7): 673–80. July 2004. doi:10.1038/ncb1142. PMID 15181449. 
  8. ↑ "POT1 as a terminal transducer of TRF1 telomere length control". Nature 423 (6943): 1013–8. June 2003. doi:10.1038/nature01688. PMID 12768206. 
  9. ↑ "POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia". Nature Genetics 45 (5): 526–30. May 2013. doi:10.1038/ng.2584. PMID 23502782. 
  10. ↑ "POT1 loss-of-function variants predispose to familial melanoma". Nature Genetics 46 (5): 478–481. May 2014. doi:10.1038/ng.2947. PMID 24686849. 
  11. ↑ "Germline mutations in shelterin complex genes are associated with familial glioma". Journal of the National Cancer Institute 107 (1): 384. January 2015. doi:10.1093/jnci/dju384. PMID 25482530. 

Further reading




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