Alternative titles; symbols
HGNC Approved Gene Symbol: PINX1
Cytogenetic location: 8p23.1 Genomic coordinates (GRCh38): 8:10,764,961-10,839,875 (from NCBI)
To identify PIN2 (TRF1; 600951)-binding proteins, Zhou and Lu (2001) screened a HeLa cell yeast 2-hybrid cDNA library using PIN2 as bait. One of the interacting proteins they identified, PINX1, was found to inhibit telomerase activity and affect tumorigenicity. The predicted 328-amino acid PINX1 protein has a gly-rich region in its N terminus and a telomerase (see TERT, 187270) inhibitory domain (TID) in its C terminus. Northern blot analysis detected a 1.9-kb PINX1 transcript in all tissues tested. Immunoprecipitation and immunoblot analyses indicated that PINX1 encodes a 45-kD protein in cells.
Zhou and Lu (2001) showed that PINX1 and its small TID bind the telomerase catalytic subunit TERT and potently inhibit its activity. Overexpression of PINX1 or its TID inhibited telomerase activity, shortened telomeres, and induced crisis, whereas depletion of endogenous PINX1 increased telomerase activity and elongated telomeres. Depletion of PINX1 also increased tumorigenicity in nude mice, consistent with its localization at 8p23, a region with frequent loss of heterozygosity in a number of human cancers. The authors concluded that PINX1 is a potent telomerase inhibitor and a putative tumor suppressor.
The 6-protein mammalian telomere protection complex shelterin contains the closely related proteins TRF1 (600951) and TRF2 (602027), which recruit various proteins to telomeres. Chen et al. (2008) demonstrated that the TRF homology domain of TRF1, but not of TRF2, interacts with the shelterin-associated factor PINX1.
By genomic sequence analysis, Zhou and Lu (2001) mapped the PINX1 gene to chromosome 8p23, a region with frequent loss of heterozygosity in several cancers.
Chen, Y., Yang, Y., van Overbeek, M., Donigian, J. R., Baciu, P., de Lange, T., Lei, M. A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins. Science 319: 1092-1096, 2008. [PubMed: 18202258] [Full Text: https://doi.org/10.1126/science.1151804]
Zhou, X. Z., Lu, K. P. The Pin2/TRF-1-interacting protein PinX1 is a potent telomerase inhibitor. Cell 107: 347-359, 2001. [PubMed: 11701125] [Full Text: https://doi.org/10.1016/s0092-8674(01)00538-4]