Increased stability of nucleolar PinX1 in the presence of TERT

Abstract

PinX1, a nucleolar protein of 328 amino acids, inhibits telomerase activity, which leads to the shortening of telomeres. The C-terminal region of PinX1 is responsible for its nucleolar localization and binding with TERT, a catalytic component of telomerase. A fraction of TERT localizes to the nucleolus, but the role of TERT in the nucleolus is largely unknown. Here, we report a functional connection between PinX1 and TERT regarding PinX1 stability. The Cterminal of PinX1205-328, a nucleolar fragment, was much more stable than the N-terminal of PinX11-204, a nuclear fragment. Interestingly, PinX1 was less stable in TERTdepleted cells and more stable in TERT-myc expressing cells. Stability assays for PinX1 truncation forms showed that both PinX11-328 and PinX1205-328, nucleolar forms, were more rapidly degraded in TERT-depleted cells, while they were more stably maintained in TERT-overexpressing cells, compared to each of the controls. However, PinX11-204 was degraded regardless of the TERT status. These results reveal that the stability of PinX1 is maintained in nucleolus in the presence of TERT and suggest a role of TERT in the regulation of PinX1 steady-state levels.