Biology:ACD (gene)
 Generic protein structure example |
Adrenocortical dysplasia protein homolog is a protein that in humans is encoded by the ACD gene.[1][2][3]
Function
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 facilitates 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] TPP1 is both necessary and sufficient to recruit the telomerase enzyme to telomeres, and is the only shelterin protein in direct contact with telomerase.[7]
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.[8] TPP1 has also been demonstrated as the only pathway required for recruitment of telomerase to chromosome ends, and it also defines telomere length homeostasis in hESCs.[8]
Interactions
ACD (gene) has been shown to interact with POT1[1][2][9] and TINF2.[1][2]
References
- ↑ 1.0 1.1 1.2 "POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex". Genes Dev 18 (14): 1649–54. July 2004. doi:10.1101/gad.1215404. PMID 15231715.
- ↑ 2.0 2.1 2.2 "PTOP interacts with POT1 and regulates its localization to telomeres". Nat Cell Biol 6 (7): 673–80. July 2004. doi:10.1038/ncb1142. PMID 15181449.
- ↑ 3.0 3.1 "Entrez Gene: ACD adrenocortical dysplasia homolog (mouse)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=65057.
- ↑ "Modern genome editing meets telomeres: the many functions of TPP1". Genes & Development 28 (17): 1857–8. September 2014. doi:10.1101/gad.250316.114. PMID 25184673.
- ↑ 5.0 5.1 "Telomere protection by mammalian Pot1 requires interaction with Tpp1". Nature Structural & Molecular Biology 14 (8): 754–61. August 2007. doi:10.1038/nsmb1270. PMID 17632522.
- ↑ 6.0 6.1 "The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity". Nature 492 (7428): 285–9. December 2012. doi:10.1038/nature11648. PMID 23103865. Bibcode: 2012Natur.492..285N.
- ↑ "Molecular mechanisms of telomere biology disorders". Journal of Biological Chemistry 296: 100064. 2021. doi:10.1074/jbc.REV120.014017. PMID 33482595.
- ↑ 8.0 8.1 "Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation". Genes & Development 28 (17): 1885–99. September 2014. doi:10.1101/gad.246819.114. PMID 25128433.
- ↑ "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. Bibcode: 2005Natur.437.1173R.
- ↑ "In vivo stoichiometry of shelterin components". The Journal of Biological Chemistry 285 (2): 1457–67. January 2010. doi:10.1074/jbc.M109.038026. PMID 19864690.
- ↑ 11.0 11.1 11.2 "A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly". Proceedings of the National Academy of Sciences of the United States of America 103 (32): 11874–9. August 2006. doi:10.1073/pnas.0605303103. PMID 16880378. Bibcode: 2006PNAS..10311874O.
- ↑ "Functional interaction between telomere protein TPP1 and telomerase". Genes & Development 24 (6): 613–22. March 2010. doi:10.1101/gad.1881810. PMID 20231318.
External links
- Human ACD genome location and ACD gene details page in the UCSC Genome Browser.
- Human TPP1 genome location and TPP1 gene details page in the UCSC Genome Browser.
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Adrenocortical dysplasia protein homolog
Further reading
- "Shelterin: the protein complex that shapes and safeguards human telomeres.". Genes Dev. 19 (18): 2100–10. 2005. doi:10.1101/gad.1346005. PMID 16166375.
- "Inside the mammalian telomere interactome: regulation and regulatory activities of telomeres.". Crit. Rev. Eukaryot. Gene Expr. 16 (2): 103–18. 2006. doi:10.1615/critreveukargeneexpr.v16.i2.10. PMID 16749892.
- "Telomerase unplugged.". ACS Chem. Biol. 2 (3): 155–8. 2007. doi:10.1021/cb700037c. PMID 17373762.
- "A "double adaptor" method for improved shotgun library construction.". Anal. Biochem. 236 (1): 107–13. 1996. doi:10.1006/abio.1996.0138. PMID 8619474.
- "Large-scale concatenation cDNA sequencing.". Genome Res. 7 (4): 353–8. 1997. doi:10.1101/gr.7.4.353. PMID 9110174.
- "A dynamic molecular link between the telomere length regulator TRF1 and the chromosome end protector TRF2.". Curr. Biol. 14 (18): 1621–31. 2005. doi:10.1016/j.cub.2004.08.052. PMID 15380063.
- "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. 2005. doi:10.1093/hmg/ddi011. PMID 15537664.
- "IMAGe association and congenital adrenal hypoplasia: no disease-causing mutations found in the ACD gene.". Mol. Genet. Metab. 88 (1): 66–70. 2006. doi:10.1016/j.ymgme.2006.01.006. PMID 16504561.
- "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.". Cell 125 (4): 801–14. 2006. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
- "A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly.". Proc. Natl. Acad. Sci. U.S.A. 103 (32): 11874–9. 2006. doi:10.1073/pnas.0605303103. PMID 16880378. Bibcode: 2006PNAS..10311874O.
- "TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase.". Nature 445 (7127): 559–62. 2007. doi:10.1038/nature05469. PMID 17237767. Bibcode: 2007Natur.445..559X.
- "The POT1-TPP1 telomere complex is a telomerase processivity factor.". Nature 445 (7127): 506–10. 2007. doi:10.1038/nature05454. PMID 17237768. Bibcode: 2007Natur.445..506W. https://deepblue.lib.umich.edu/bitstream/2027.42/62923/1/nature05454.pdf.
- "The POT1-TPP1 telomere complex is a telomerase processivity factor.". Nature 445 (7127): 506–10. 2007. doi:10.1038/nature05454. PMID 17237768. Bibcode: 2007Natur.445..506W. https://deepblue.lib.umich.edu/bitstream/2027.42/62923/1/nature05454.pdf.
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