The Pin2/TRF1-interacting: Protein PinX1 is a potent telomerase inhibitor

Authors
Citation
Xz. Zhou et Kp. Lu, The Pin2/TRF1-interacting: Protein PinX1 is a potent telomerase inhibitor, CELL, 107(3), 2001, pp. 347-359
Citations number
71
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL
ISSN journal
0092-8674 → ACNP
Volume
107
Issue
3
Year of publication
2001
Pages
347 - 359
Database
ISI
SICI code
0092-8674(20011102)107:3<347:TPPPIA>2.0.ZU;2-S
Abstract
Telomerase activity is critical for normal and transformed human cells to e scape from crisis and is implicated in oncogenesis. Here we describe a nove l Pin2/TRF1 binding protein, PinX1 that inhibits telomerase activity and af fects tumorigenicity. PinX1 and its small TID domain bind the telomerase ca talytic subunit hTERT and potently inhibit its activity. Overexpression of PinX1 or its TID domain inhibits telomerase activity, shortens telomeres, a nd induces crisis:, whereas depletion of endogenous PinX1 increases telomer ase activity and elongates telomeres. Depletion of PinX1 also increases tum origenicity in nude mice, consistent with its chromosome localization at 8p 23, a region with frequent loss of heterozygosity in a number of human canc ers. Thus, PinX1 is a potent telomerase inhibitor and a putative tumor supp ressor.