Adrenocortical dysplasia protein homolog is a protein that in humans is encoded by the ACDgene.[5][6][7]
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.[7]
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.[8] 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,[9] more recent studies suggest that TPP1 could directly promotes telomerase activity at the telomere.[10] TPP1 is both necessary and sufficient to recruit the telomerase enzyme to telomeres, and is the only shelterin protein in direct contact with telomerase.[11]
A part of the TPP1 oligonucleotide/oligosaccharide-binding fold named TEL patch that interacts with the catalytic subunit of telomerase, hTERT, has been proven essential for telomerase activation.[12] 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.[12]
^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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID16189514. S2CID4427026.
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.
