This gene encodes a protein that is involved in telomere function. This protein is one of six core proteins in the telosome/shelterin telomeric complex, which functions to maintain telomere length and to protect telomere ends. Through its interaction with other components, this protein plays a key role in the assembly and stabilization of this complex, and it mediates the access of telomerase to the telomere. Multiple transcript variants encoding different isoforms have been found for this gene. This gene, which is also referred to as TPP1, is distinct from the unrelated TPP1 gene on chromosome 11, which encodes tripeptidyl-peptidase I.[3]
TPP1 is a component of the telomere-specific shelterin complex, which facilitats the replication of the double-stranded telomeric DNA tracts and protects the telomeric end from unregulated DNA repair activities. TPP1 mainly functions as a regulator of telomerase recruitment, activation, and regulation.[4] Although TPP1 was originally described as a bridging factor between TRF1 and TRF2, which participate in a pathway with POT1 as a negative regulator of telomerase-dependent telomere length control, [5] more recent studies suggest that TPP1 could directly promotes telomerase activity at the telomere.[6] A part of the TPP1 oligonucleotide/oligosaccharide-binding (OB) fold named TEL patch that interacts with the catalytic subunit of telomerase, hTERT, has been proven essential for telomerase activation.[7] What’s more, TPP1 has been demonstrated the only pathway required for recruitment of telomerase to chromosome ends, and it also defines telomere length homeostasis in hESCs.[7]
↑ 2.02.12.2Liu 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". Nat Cell Biol. 6 (7): 673–80. doi:10.1038/ncb1142. PMID15181449.
↑Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
de Lange T (2005). "Shelterin: the protein complex that shapes and safeguards human telomeres". Genes Dev. 19 (18): 2100–10. doi:10.1101/gad.1346005. PMID16166375.
Songyang Z, Liu D (2006). "Inside the mammalian telomere interactome: regulation and regulatory activities of telomeres". Crit. Rev. Eukaryot. Gene Expr. 16 (2): 103–18. doi:10.1615/critreveukargeneexpr.v16.i2.10. PMID16749892.
Houghtaling BR, Cuttonaro L, Chang W, Smith S (2005). "A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2". Curr. Biol. 14 (18): 1621–31. doi:10.1016/j.cub.2004.08.052. PMID15380063.
Keegan CE, Hutz JE, Else T, Adamska M, Shah SP, Kent AE, Howes JM, Beamer WG, Hammer GD (2005). "Urogenital and caudal dysgenesis in adrenocortical dysplasia (acd) mice is caused by a splicing mutation in a novel telomeric regulator". Hum. Mol. Genet. 14 (1): 113–23. doi:10.1093/hmg/ddi011. PMID15537664.
Hutz JE, Krause AS, Achermann JC, Vilain E, Tauber M, Lecointre C, McCabe ER, Hammer GD, Keegan CE (2006). "IMAGe association and congenital adrenal hypoplasia: no disease-causing mutations found in the ACD gene". Mol. Genet. Metab. 88 (1): 66–70. doi:10.1016/j.ymgme.2006.01.006. PMID16504561.
Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID16713569.
Xin H, Liu D, Wan M, Safari A, Kim H, Sun W, O'Connor MS, Songyang Z (2007). "TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase". Nature. 445 (7127): 559–62. doi:10.1038/nature05469. PMID17237767.
