Abstract
PIN2/TRF1-interacting telomerase inhibitor 1 (PinX1) is a novel cloned gene located at human chromosome 8p23, playing a vital role in maintaining telomeres length and chromosome stability. It has been demonstrated to be involved in tumor genesis and progression in most malignancies. However, some researches showed opposing molecular status of PinX1 gene and its expression patterns in several other types of tumors. The pathogenic mechanism of PinX1 expression in human malignancy is not yet clear. Moreover, emerging evidence suggest that PinX1 (especially its TID domain) might be a potential new target cancer treatment. Therefore, PinX1 may be a new potential diagnostic biomarker and therapeutic target for human cancers, and may play different roles in different human cancers. The functions and the mechanisms of PinX1 in various human cancers remain unclear, suggesting the necessity of further extensive works of its role in tumor genesis and progression.
Highlights
The ability of telomerase to elongate telomeres is regulated by a specialized protein complex, called shelterin www.impactjournals.com/oncotarget or telosome, which binds to and protects telomeres at chromosome ends [27, 28]
This complex is able to interact with a variety of other proteins by its three telomeric DNA-binding proteins (TRF1, TRF2 and protection of telomeres-1 (POT1)), referred to as the telomere interactome, in order to fulfill their biological functions and control signaling cascades originating from telomeres [31, 32]
Besides its binding to and inhibition of telomerase, other mechanisms of these functions been found, for example: the regulation of telomerase activity by PinX1 in gastric cancer is involved in Mad/c-Myc pathway [84], and the role of PinX1 in telomerase function regulation is mediated by cycle-dependent localization of telomerase to telomere [85]
Summary
The ability of telomerase to elongate telomeres is regulated by a specialized protein complex, called shelterin www.impactjournals.com/oncotarget or telosome, which binds to and protects telomeres at chromosome ends [27, 28]. The 290-328 aa region which contains a PinX1 nucleolus localization signal can associate with TERT, it is essential for the inhibition of telomerase activity [37]. PinX1 can potently inhibit telomerase activation and telomeres elongation in cancer cells [35, 44], this ability is conserved in yeast, rats and zebra fish [45,46,47].
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