title: XAB2 functions in mitotic cell cycle progression via transcriptional regulation of CENPE.
abstract: Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is a multi-functional protein that plays critical role in processes including transcription, transcription-coupled DNA repair, pre-mRNA splicing, homologous recombination and mRNA export. Microarray analysis on gene expression in XAB2 knockdown cells reveals that many genes with significant change in expression function in mitotic cell cycle regulation. Fluorescence-activated cell scanner analysis confirmed XAB2 depletion led to cell arrest in G2/M phase, mostly at prophase or prometaphase. Live cell imaging further disclosed that XAB2 knockdown induced severe mitotic defects including chromosome misalignment and defects in segregation, leading to mitotic arrest, mitotic catastrophe and subsequent cell death. Among top genes down-regulated by XAB2 depletion is mitotic motor protein centrosome-associated protein E (CENPE). Knockdown CENPE showed similar phenotypes to loss of XAB2, but CENPE knockdown followed by XAB2 depletion did not further enhance cell cycle arrest. Luciferase assay on CENPE promoter showed that overexpression of XAB2 increased luciferase activity, whereas XAB2 depletion resulted in striking reduction of luciferase activity. Further mapping revealed a region in CENPE promoter that is required for the transcriptional regulation by XAB2. Moreover, ChIP assay showed that XAB2 interacted with CENPE promoter. Together, these results support a novel function of XAB2 in mitotic cell cycle regulation, which is partially mediated by transcription regulation on CENPE.
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Wei
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Hao
authors.affiliation: Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Sikandar
authors.initials: S
authors.lastname: Azam
authors.affiliation: Breast Disease and Reconstruction Center, Breast Cancer Key Lab of Dalian, Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Caigang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Bilian
authors.initials: B
authors.lastname: Jin
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.|Department of Oncology, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors.forename: Haixin
authors.initials: H
authors.lastname: Lei
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics; D053960:DNA Breaks; D017353:Gene Deletion; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D000072260:RNA Splicing Factors; D008941:Spindle Apparatus / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D000072260:RNA Splicing Factors; D014157:Transcription Factors; C417244:XAB2 protein, human; C068688:centromere protein E