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Increased Stability of Nucleolar PinX1 in the Presence of TERT.

Keo P, Choi JS, Bae J, Shim YH, Oh BK - Mol. Cells (2015)

Bottom Line: Interestingly, PinX1 was less stable in TERT-depleted cells and more stable in TERT-myc expressing cells.However, PinX1(1-204) 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.

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 C-terminal of PinX1(205-328), a nucleolar fragment, was much more stable than the N-terminal of PinX1(1-204), a nuclear fragment. Interestingly, PinX1 was less stable in TERT-depleted cells and more stable in TERT-myc expressing cells. Stability assays for PinX1 truncation forms showed that both PinX1(1-328) and PinX1(205-328), 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, PinX1(1-204) 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.

No MeSH data available.


A proposed model of the accumulation of PinX1 in the nucleolus. TERT increases the stability of PinX1, which results in the accumulation of PinX1 in the nucleolus. Accumulated PinX1 sequesters TERT in the nucleolus, which may impair telomere elongation.
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f6-molce-38-9-814: A proposed model of the accumulation of PinX1 in the nucleolus. TERT increases the stability of PinX1, which results in the accumulation of PinX1 in the nucleolus. Accumulated PinX1 sequesters TERT in the nucleolus, which may impair telomere elongation.

Mentions: PinX1 was rapidly degraded in TERT-depleted cells, and stably maintained under conditions of excess TERT. This effect, however, was not evident in a nuclear form of PinX1. We found that the subcellular localization of PinX1 was not altered by TERT, which indicates that the nucleolar localization of PinX1 is independent of TERT. Our findings reveal that TERT does not control PinX1 localization to nucleolus but has an effect on the stability of nucleolar PinX1. These led us to speculate that functional interaction between PinX1 and TERT takes place in the nucleolus. Given that the C-terminal of PinX1 is responsible for TERT binding and nucleolar localization (Chen et al., 2010), PinX1 may gain stability in the nucleolus through interaction of the C-terminal region with TERT (Fig. 6). However, it is not clear yet whether the observed effects could result from a direct stabilization of PinX1 by TERT, or alternatively indirect mechanisms. To provide more convincing evidence that TERT directly promotes PinX1 stabilization, the physical association between TERT and PinX1 needs to be examined using co-immunoprecipitation whether it increases upon TERT overexpression.


Increased Stability of Nucleolar PinX1 in the Presence of TERT.

Keo P, Choi JS, Bae J, Shim YH, Oh BK - Mol. Cells (2015)

A proposed model of the accumulation of PinX1 in the nucleolus. TERT increases the stability of PinX1, which results in the accumulation of PinX1 in the nucleolus. Accumulated PinX1 sequesters TERT in the nucleolus, which may impair telomere elongation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588725&req=5

f6-molce-38-9-814: A proposed model of the accumulation of PinX1 in the nucleolus. TERT increases the stability of PinX1, which results in the accumulation of PinX1 in the nucleolus. Accumulated PinX1 sequesters TERT in the nucleolus, which may impair telomere elongation.
Mentions: PinX1 was rapidly degraded in TERT-depleted cells, and stably maintained under conditions of excess TERT. This effect, however, was not evident in a nuclear form of PinX1. We found that the subcellular localization of PinX1 was not altered by TERT, which indicates that the nucleolar localization of PinX1 is independent of TERT. Our findings reveal that TERT does not control PinX1 localization to nucleolus but has an effect on the stability of nucleolar PinX1. These led us to speculate that functional interaction between PinX1 and TERT takes place in the nucleolus. Given that the C-terminal of PinX1 is responsible for TERT binding and nucleolar localization (Chen et al., 2010), PinX1 may gain stability in the nucleolus through interaction of the C-terminal region with TERT (Fig. 6). However, it is not clear yet whether the observed effects could result from a direct stabilization of PinX1 by TERT, or alternatively indirect mechanisms. To provide more convincing evidence that TERT directly promotes PinX1 stabilization, the physical association between TERT and PinX1 needs to be examined using co-immunoprecipitation whether it increases upon TERT overexpression.

Bottom Line: Interestingly, PinX1 was less stable in TERT-depleted cells and more stable in TERT-myc expressing cells.However, PinX1(1-204) 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.

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 C-terminal of PinX1(205-328), a nucleolar fragment, was much more stable than the N-terminal of PinX1(1-204), a nuclear fragment. Interestingly, PinX1 was less stable in TERT-depleted cells and more stable in TERT-myc expressing cells. Stability assays for PinX1 truncation forms showed that both PinX1(1-328) and PinX1(205-328), 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, PinX1(1-204) 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.

No MeSH data available.