title: A regulatory effect of INMAP on centromere proteins: antisense INMAP induces CENP-B variation and centromeric halo.
abstract: CENP-B is a highly conserved protein that facilitates the assembly of specific centromere structures both in interphase nuclei and on mitotic chromosomes. INMAP is a conserved protein that localizes at nucleus in interphase cells and at mitotic apparatus in mitotic cells. Our previous results showed that INMAP over-expression leads to spindle defects, mitotic arrest and formation of polycentrosomal and multinuclear cells, indicating that INMAP may modulate the function of (a) key protein(s) in mitotic apparatus. In this study, we demonstrate that INMAP interacts with CENP-B and promotes cleavage of the N-terminal DNA binding domain from CENP-B. The cleaved CENP-B cannot associate with centromeres and thus lose its centromere-related functions. Consistent with these results, CENP-B in INMAP knockdown cells becomes more diffused around kinetochores. Although INMAP knockdown cells do not exhibit gross defects in mitotic spindle formation, these cells go through mitosis, especially prophase and metaphase, with different relative timing, indicating subtle abnormality. These results identify INMAP as a model regulator of CENP-B and support the notion that INMAP regulates mitosis through modulating CENP-B-mediated centromere organization.
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Tan
authors.initials: T
authors.lastname: Tan
authors.affiliation: Beijing Key Laboratory of Gene Resource and Molecular Development / Beijing Key Laboratory of Gene Engineering Drugs & Biological Technology, Beijing Normal University, Beijing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China; Beijing Key Laboratory of Gene Resource and Molecular Development / Beijing Key Laboratory of Gene Engineering Drugs & Biological Technology, Beijing Normal University, Beijing, China.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Liang
mesh_terms: D021581:Active Transport, Cell Nucleus; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism*; D051936:Centromere Protein B / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis
chemical_list: D018797:Cell Cycle Proteins; D051936:Centromere Protein B; C540368:INMAP protein, human; D009687:Nuclear Proteins; D004247:DNA