Adrenocortical dysplasia protein homolog

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.

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. 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, more recent studies suggest that TPP1 could directly promotes telomerase activity at the telomere. TPP1 is both necessary and sufficient to recruit the telomerase enzyme to telomeres, and is the only shelterin protein in direct contact with telomerase.

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. 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.

Interactions

ACD (gene) has been shown to interact with POT1 and TINF2.

• POT1
• hTERT
• TIN2
• TRF1
• TRF2
• Telomerase

References

References

1. (July 2004). "POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex". Genes Dev.
2. (July 2004). "PTOP interacts with POT1 and regulates its localization to telomeres". Nat Cell Biol.
3. "Entrez Gene: ACD adrenocortical dysplasia homolog (mouse)".
4. (September 2014). "Modern genome editing meets telomeres: the many functions of TPP1". Genes & Development.
5. (August 2007). "Telomere protection by mammalian Pot1 requires interaction with Tpp1". Nature Structural & Molecular Biology.
6. (December 2012). "The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity". Nature.
7. (2021). "Molecular mechanisms of telomere biology disorders". [[Journal of Biological Chemistry]].
8. (September 2014). "Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation". Genes & Development.
9. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". [[Nature (journal).
10. (January 2010). "In vivo stoichiometry of shelterin components". The Journal of Biological Chemistry.
11. (August 2006). "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.
12. (March 2010). "Functional interaction between telomere protein TPP1 and telomerase". Genes & Development.