2017
DOI: 10.1038/ncomms14059
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A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity

Abstract: Tumour radiotherapy resistance involves the cell cycle pathway. CDC25 phosphatases are key cell cycle regulators. However, how CDC25 activity is precisely controlled remains largely unknown. Here, we show that LIM domain-containing proteins, such as FHL1, increase inhibitory CDC25 phosphorylation by forming a complex with CHK2 and CDC25, and sequester CDC25 in the cytoplasm by forming another complex with 14-3-3 and CDC25, resulting in increased radioresistance in cancer cells. FHL1 expression, induced by ioni… Show more

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Cited by 51 publications
(51 citation statements)
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“…Because mitotic catastrophe is an important mechanism of cell death in solid tumors receiving clinical radiotherapy, we next assessed mitotic catastrophe after a 4‐Gy dose of XRT or PRT in our 4 HNSCC cell lines by co‐staining the cytoplasm for γ‐tubulin (with Texas Red) and the nucleus with DAPI (blue) and noting morphologic changes in the nuclei . The percentages of cells in mitotic catastrophe in the control conditions ranged from 11.45% (±4.55) to 29.54% (±2.46).…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…Because mitotic catastrophe is an important mechanism of cell death in solid tumors receiving clinical radiotherapy, we next assessed mitotic catastrophe after a 4‐Gy dose of XRT or PRT in our 4 HNSCC cell lines by co‐staining the cytoplasm for γ‐tubulin (with Texas Red) and the nucleus with DAPI (blue) and noting morphologic changes in the nuclei . The percentages of cells in mitotic catastrophe in the control conditions ranged from 11.45% (±4.55) to 29.54% (±2.46).…”
Section: Resultsmentioning
confidence: 99%
“…Immunoreactions were visualized with a Leica Microsystem (Wetzlar, Germany) at ×100 magnification, and cells were photographed in at least 10 randomly chosen fields. Cells with multinucleated enlarged nuclei, complete aberrant nuclei, prematurely condensed chromosomes without cytoplasm shrinkage and nuclear fragmentation, multiple micronuclei, catastrophic clusters, and nuclei undergoing multinucleation were considered to be in mitotic catastrophe . Those cells in mitotic catastrophe were counted as a percentage of all cells, and the results are shown as the average percentages from 3 independent experiments.…”
Section: Methodsmentioning
confidence: 99%
“…At the different time points, the two rats were sacrificed and full‐thickness skin samples including intact skin adjacent to the wound, the wound margin and epithelialized wounds were collected and prepared as tissue slices. Slices were then examined using HE (hematoxylin and eosin) and Sirius Red staining …”
Section: Methodsmentioning
confidence: 99%
“…Quantitative real-time PCR (qPCR) was performed following the methods described in references. 35,36 The level of β-actin mRNA was measured as a loading control. Primers used in qPCR experiments are listed in Table 1.…”
Section: Quantitative Polymerase Chain Reactionmentioning
confidence: 99%