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Human PinX1 mediates TRF1 accumulation in nucleolus and enhances TRF1 binding to telomeres

Authors
 Jeong Eun Yoo  ;  Bong-Kyeong Oh  ;  Young Nyun Park 
Citation
 JOURNAL OF MOLECULAR BIOLOGY, Vol.388(5) : 928-940, 2009 
Journal Title
 JOURNAL OF MOLECULAR BIOLOGY 
ISSN
 0022-2836 
Issue Date
2009
MeSH
Animals ; Cell Cycle/physiology ; Cell Nucleolus/metabolism* ; Cell Nucleus/metabolism ; HeLa Cells ; Humans ; Mice ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Telomere/metabolism* ; Telomeric Repeat Binding Protein 1/chemistry ; Telomeric Repeat Binding Protein 1/genetics ; Telomeric Repeat Binding Protein 1/metabolism* ; Tumor Suppressor Proteins/chemistry ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism*
Keywords
human PinX1 ; TRF1 ; nucleolus ; telomere ; ALT
Abstract
Human PinX1 (hPinX1) is known to interact with telomere repeat binding factor 1 (TRF1) and telomerase. Here, we report that hPinX1 regulates the nucleolar accumulation and telomeric association of TRF1. In HeLa, HA-hPinX1 was co-localized with fibrillarin, a nucleolar protein, in 51% of the transfected cells and was present in the nucleoplasm of the remaining 48%. Mutant analysis showed that the C-terminal region was important for nucleolar localization, while the N-terminus exhibited an inhibitory effect on nucleolar localization. Unlike HA- and Myc-hPinX1, GFP-hPinX1 resided predominantly in the nucleolus. Nuclear hPinX1 bound to telomeres and other repeat sequences as well but, despite its interaction with TRF1, nucleolar hPinX1 did not bind to telomeres. Nucleolar hPinX1 forced endogenous TRF1 accumulation in the nucleolus. Furthermore, TRF1 binding to telomeres was upregulated in cells over-expressing hPinX1. In an ALT cell line, WI-38 VA-13, TRF1 did not co-localize with hPinX1 in the nucleoli. In summary, hPinX1 likely interacts with TRF1 in both the nucleolus and the nucleoplasm, and excess hPinX1 results in increased telomere binding of TRF1. The PinX1 function of mediating TRF1 nucleolar accumulation is absent from ALT cells, suggesting that it might be telomerase-dependent
Full Text
http://www.sciencedirect.com/science/article/pii/S0022283609002034
DOI
10.1016/j.jmb.2009.02.051
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Oh, Bong Kyeong(오봉경)
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103896
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