XAB2 functions in mitotic cell cycle progression via transcriptional regulation of CENPE

Hou, Shuai; Li, Na; Zhang, Qian; Li, Hui; Wei, Xinyue; Hao, Tian; Li, Yue; Azam, Sikandar; Liu, Caigang; Cheng, Wei; Jin, Bilian; Liu, Quentin; Li, Man; Lei, Hetian

doi:10.1038/cddis.2016.313

Cited by 35 publications

(43 citation statements)

References 50 publications

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“…Depletion of XAB2 leads to defective NER. Previous ndings revealed that XAB2 is involved in the transcription-coupled sub-pathway of NER (TC-NER) 18,29 . To test for the functional role of XAB2 in NER, we carried a series of pulldown assays in nuclear extracts of UV-irradiated (10J/m 2 ) and control bXAB2 primary mouse embryonic broblasts (MEFs).…”

Section: Resultsmentioning

confidence: 99%

The Splicing Factor XAB2 interacts with ERCC1-XPF and XPG for RNA-loop processing during mammalian development

Goulielmaki

Tsekrekou

Batsiotos

et al. 2020

Preprint

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RNA splicing, transcription and the DNA damage response are intriguingly linked in mammals but the underlying mechanisms remain poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the splicing factor XAB2 interacts with the core spliceosome and that it binds to spliceosomal U4 and U6 snRNAs and pre-mRNAs in developing livers. XAB2 depletion leads to aberrant intron retention, R-loop formation and DNA damage in cells. Studies in illudin S-treated cells and Csbm/m developing livers reveal that transcription-blocking DNA lesions trigger the release of XAB2 from all RNA targets tested. Immunoprecipitation studies reveal that XAB2 interacts with ERCC1-XPF and XPG endonucleases outside nucleotide excision repair and that the trimeric protein complex binds RNA:DNA hybrids under conditions that favor the formation of R-loops. Thus, XAB2 functionally links the spliceosomal response to DNA damage with R-loop processing with important ramifications for mammalian development and transcription-coupled DNA repair disorders.

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Section: Resultsmentioning

confidence: 99%

The Splicing Factor XAB2 interacts with ERCC1-XPF and XPG for RNA-loop processing during mammalian development

Goulielmaki

Tsekrekou

Batsiotos

et al. 2020

Preprint

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“…However, the role RRM2 plays in the development of cSCC is unclear. The protein encoded by CENPE is a forward-directed kinesin, belonging to the kinesin-7 subfamily, which is critical in mitosis [39]. Increasing evidence shows that CENPE may be a useful drug target for several tumors without targeted therapy [40].…”

Section: Discussionmentioning

confidence: 99%

Screening and Identification of Novel Biomarkers Associated with Cutaneous Squamous Cell Carcinoma

Huang

Han

et al. 2020

Preprint

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Background: Cutaneous squamous cell carcinoma (cSCC) is the leading cause of death in patients with non-melanoma skin cancers (NMSC). However, unclear pathogenesis of cSCC limits the application of molecular targeted therapy. Results: To identify the hub genes in the pathogenesis and progression of cSCC, we downloaded the microarray data sets GSE2503, GSE45164 and GSE66359 from the Gene Expression Omnibus (GEO) database, and identified differentially expressed genes (DEGs) between tumor and non-tumor tissues. Functional enrichment analysis was performed using DAVID. The STRING online website was used to construct a protein-protein interaction network (PPI), and then Cytoscape performed module analysis and degree calculation. 146 DEGs were identified with significant differences, including 113 up-regulated genes and 33 down-regulated genes. The enriched functions and pathways of the DEGs include microtubule-based movement, ATP binding, cell cycle, p53 signaling pathway, oocyte meiosis and PLK1 signaling events. Nine hub genes were identified, namely CDK1, AURKA, RRM2, CENPE, CCNB1, KIAA0101, ZWINT, TOP2A, ASPM. The differential expression of these genes has been verified in other data sets. In addition, the ROC curve also confirmed their ability to predict disease. Conclusion: By integrated bioinformatic analysis, the DEGs and hub genes identified in this study elucidated the molecular mechanism of the pathogenesis and progression of cSCC, and are expected to become future biomarkers or therapeutic targets.

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“…CENPE is one of major spindle checkpoint genes and regulates the cell cycle. Down-regulation of CENPE leads to chromosome misalignment and delayed mitotic progression [29]. However, the clinical correlations and roles of CENPE in cancer are not quite clear at present.…”

Section: Discussionmentioning

confidence: 99%

Proteomic alterations of fibroblasts induced by ovarian cancer cells reveal potential cancer targets

Zhang¹,

Hong²,

Zhang³

et al. 2018

neo

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The common spread pattern of ovarian cancer is peritoneal implantation. The growth of the shed ovarian cancer cells in the peritoneal cavity is closely related to the tumor microenvironment. Cancer-associated fibroblasts are vital in the tumor microenvironment. It is not clearly defined that the protein expression alters during the activating process of fibroblasts. This study detected the protein alterations in fibroblasts induced by ovarian cancer cells and explored the potential biological relevance through two-dimensional gel electrophoresis and mass spectrometry. Our data showed that the level of CENPE, BAG2, SOD2, GDI2, CORO1C, CFL1, DSTN, CALD1, PHGDH, PDHA1, AKR1B1, TST and TBCA proteins were significantly up-regulated in the fibroblasts co-cultured with ovarian cancer cells, whereas HSPB1, P4HB and VIM were significantlydown-regulated. However, only BAG2, SOD2 and CORO1C proteins were confirmed to be significantly increased by western blot analysis. The differentially expressed proteins were mainly involved in metabolic processes, cellular component organization, responses to stimulus, multicellular organismal processes, localization, protein depolymerization, cellular senescence and the mitotic pathway. These data demonstrated that fibroblasts had an altered protein expression pattern after being induced by ovarian cancer cells, and participated in multiple cell processes resulting in tumor progression. The differentially expressed proteins should be considered as targets for cancer treatment.

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XAB2 functions in mitotic cell cycle progression via transcriptional regulation of CENPE

Cited by 35 publications

References 50 publications

The Splicing Factor XAB2 interacts with ERCC1-XPF and XPG for RNA-loop processing during mammalian development

The Splicing Factor XAB2 interacts with ERCC1-XPF and XPG for RNA-loop processing during mammalian development

Screening and Identification of Novel Biomarkers Associated with Cutaneous Squamous Cell Carcinoma

Proteomic alterations of fibroblasts induced by ovarian cancer cells reveal potential cancer targets

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