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ZSCAN4 and TRF1: A functionally indirect interaction in cancer cells independent of telomerase activity.

Abstract：

PURPOSE:Recently, the newly identified embryonic stem cell marker, Zinc finger and SCAN domain containing 4 gene (ZSCAN4), which plays a key role in genomic stability by regulating telomere elongation, was shown to co-localize with TRF1 foci. This suggests that the interaction of ZSCAN4 with TRF1 functions in regulation of telomere elongation in ESC. Based on these studies, we hypothesized that ZSCAN4 binds to TRF1 in cancer cells to function in regulating telomere length. The purpose of this study was to determine whether this interaction occurred across different cell lineage-derived cancers and whether telomerase status impacted this relationship. To that end, telomerase positive cervical cancer cells (HeLa) and breast cancer cells (MCF7), and telomerase negative osteosarcoma cells (SaOS2), were analyzed for ZSCAN4 and TRF1 interactions. RESULTS:Immunocytochemistry demonstrated co-localization of ZSCAN4 and TRF1 to the nucleus. This functional relationship was confirmed using BiFC imaging analysis based on distance in situ. Co-immunoprecipitation and pull-down assay results demonstrated that ZSCAN4 binds with TRF1 in vitro indirectly. All three cell types showed similar results. CONCLUSIONS:In this study, we revealed, for the first time, that ZSCAN4 indirectly interacts with TRF1 (functional association protein) in cancer cells. Furthermore, we show that ZSCAN4 plays an important role independent of telomere maintenance pathways (telomerase positive and ALT) or cell lineage.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Lee K,Gollahon LS

doi

10.1016/j.bbrc.2015.09.107

subject

Has Abstract

pub_date

2015-10-30 00:00:00

pages

644-9

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(15)30624-0

journal_volume

466

pub_type

杂志文章

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