Shelterin complex subunit TPP1 (TPP1) (TPP1)

Shelterin complex subunit TPP1, encoded by the ACD gene, is a central component of the shelterin complex that safeguards telomeres and regulates telomerase activity (UniProt Q96AP0). It functions as a critical bridge within the complex, connecting the double-stranded DNA-binding proteins TRF1 and TRF2 to the single-stranded DNA-binding protein POT1 (PMID: 16893904). TPP1 is essential for recruiting telomerase to the telomere through its oligonucleotide/oligosaccharide-binding (OB) fold, specifically a region known as the TEL patch (PMID: 22542154). Beyond recruitment, it also stimulates telomerase processivity, enabling the addition of multiple telomeric repeats (PMID: 17513324). Mutations in TPP1 are associated with telomere biology disorders, including Dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome, which are characterized by premature aging and bone marrow failure (PMID: 25236424). Conversely, TPP1 is often overexpressed in various cancers, such as hepatocellular carcinoma, where it promotes cellular immortality by maintaining telomere length (PMID: 38313120). Consequently, TPP1 is considered a promising therapeutic target for anti-cancer drug development, with strategies aimed at disrupting its interaction with telomerase to induce senescence in malignant cells (PMID: 22542154). While no drugs are currently approved, experimental approaches include small molecules and peptides targeting the TPP1-TERT interface.

Other names

Adrenocortical dysplasia protein homologACDPOT1- and TIN2-interacting proteinPIP1PTOPTINT1DKCA6DKCB7

Inhibition of telomerase recruitment to telomeres and disruption of the shelterin complex to induce telomere uncapping and cellular senescence.