Nucleolar localization of the human telomeric repeat binding factor 2 (TRF2)

Zhang, Suisheng; Hemmerich, Peter; Grosse, Frank

doi:10.1242/jcs.01249

Cited by 51 publications

(40 citation statements)

References 43 publications

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“…This suggests a dynamic exchange of CTCF between the nucleolus and the nucleoplasm rather than the passive storage of this factor in the nucleolar compartment and also points to the existence of a protein interaction network important for CTCF translocation in the nucleolus. Similar networks have been proposed for other factors that accumulate in the nucleolus in the same way as CTCF (Desterro et al, 2003;Straight et al, 1999;Zhang et al, 2004b).…”

Section: Ctcf Accumulates In Nucleoli Of Mammalian Cells Upon Differementioning

confidence: 82%

Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism

Torrano

Navascués

Zhang

et al. 2006

Journal of Cell Science

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Multiple functions have been reported for the transcription factor and candidate tumour suppressor, CTCF. Among others, they include regulation of cell growth, differentiation and apoptosis, enhancer-blocking activity and control of imprinted genes. CTCF is usually localized in the nucleus and its subcellular distribution during the cell cycle is dynamic; CTCF was found associated with mitotic chromosomes and the midbody, suggesting different roles for CTCF at different stages of the cell cycle. Here we report the nucleolar localization of CTCF in several experimental model systems. Translocation of CTCF from nucleoplasm to the nucleolus was observed after differentiation of K562 myeloid cells and induction of apoptosis in MCF7 breast cancer cells. CTCF was also found in the nucleoli in terminally differentiated rat trigeminal ganglion neurons. Thus our data show that nucleolar localization of CTCF is associated with growth arrest. Interestingly, the 180 kDa poly(ADP-ribosyl)ated isoform of CTCF was predominantly found in the nucleoli fractions. By transfecting different CTCF deletion constructs into cell lines of different origin we demonstrate that the central zinc-finger domain of CTCF is the region responsible for nucleolar targeting. Analysis of subnucleolar localization of CTCF revealed that it is distributed homogeneously in both dense fibrillar and granular components of the nucleolus, but is not associated with fibrillar centres. RNA polymerase I transcription and protein synthesis were required to sustain nucleolar localization of CTCF. Notably, the labelling of active transcription sites by in situ run-on assays demonstrated that CTCF inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism.

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Section: Ctcf Accumulates In Nucleoli Of Mammalian Cells Upon Differementioning

confidence: 82%

Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism

Torrano

Navascués

Zhang

et al. 2006

Journal of Cell Science

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“…Although we did observe both ribosomal and hnRNP proteins in our TIN2 pulldowns, we did not observe these proteins in our HA-FLAG-GFP pulldowns, suggesting that their interaction with TIN2 was specific and not due to their high expression within the cell. Finally, the TIN2-binding protein TRF2 traffics through the nucleolus (50), and in several instances we isolated nucleolar proteins. However, we did not isolate a significant number of nucleolar proteins, arguing that the proteins that were isolated specifically interact with TIN2 possibly through TRF2.…”

Section: Discussionmentioning

confidence: 99%

Revealing Novel Telomere Proteins Using in Vivo Cross-linking, Tandem Affinity Purification, and Label-free Quantitative LC-FTICR-MS

Nittis

Guittat

LeDuc

et al. 2010

Molecular & Cellular Proteomics

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Telomeres are DNA-protein structures that protect chromosome ends from the actions of the DNA repair machinery. When telomeric integrity is compromised, genomic instability ensues. Considerable effort has focused on identification of telomere-binding proteins and elucidation of their functions. To date, protein identification has relied on classical immunoprecipitation and mass spectrometric approaches, primarily under conditions that favor isolation of proteins with strong or long lived interactions that are present at sufficient quantities to visualize by SDS-PAGE. To facilitate identification of low abundance and transiently associated telomere-binding proteins, we developed a novel approach that combines in vivo protein-protein cross-linking, tandem affinity purification, and stringent sequential endoprotease digestion. Peptides were identified by label-free comparative nano-LC-FTICR-MS. Here, we expressed an epitope-tagged telomere-binding protein and utilized a modified chromatin immunoprecipitation approach to cross-link associated proteins. The resulting immunoprecipitant contained telomeric DNA, establishing that this approach captures bona fide telomere binding complexes. To identify proteins present in the immunocaptured complexes, samples were reduced, alkylated, and digested with sequential endoprotease treatment. The resulting peptides were purified using a microscale porous graphite stationary phase and analyzed using nano-LC-FTICR-MS. Proteins enriched in cells expressing HA-FLAG-TIN2 were identified by label-free quantitative analysis of the FTICR mass spectra from different samples and ion trap tandem mass spectrometry followed by database searching. We identified all of the proteins that constitute the telomeric shelterin complex, thus validating the robustness of this approach. We also identified 62 novel telomere-binding proteins. These results demonstrate that DNA-bound protein complexes, including those present at low molar ratios, can be identified by this approach. The success of this approach will allow us to create a more complete understanding of telomere maintenance and have broad applicability. Molecular & Cellular Proteomics 9: 1144 -1156, 2010.

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“…In addition, p21 increases the cytotoxic effects of cisplatin in human hepatoma and ovarian carcinoma (22,23). Since nucleolar proteins are known to regulate genomic stability, nucleoli are critical sites for maintaining cellular homeostasis (24)(25)(26)(27). According to recent studies, nucleoli in cancer cells alter their morphology and the rate of ribosome biogenesis by neoplastic transformation (27,28).…”

Section: Discussionmentioning

confidence: 99%

Depletion of Neuroguidin/CANu1 sensitizes human osteosarcoma U2OS cells to doxorubicin

Park

Sihn²,

Lee³

et al. 2011

BMB Reports

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Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli, which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells.

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Nucleolar localization of the human telomeric repeat binding factor 2 (TRF2)

Cited by 51 publications

References 43 publications

Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism

Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism

Revealing Novel Telomere Proteins Using in Vivo Cross-linking, Tandem Affinity Purification, and Label-free Quantitative LC-FTICR-MS

Depletion of Neuroguidin/CANu1 sensitizes human osteosarcoma U2OS cells to doxorubicin

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