2. Academic Validation
  3. C9ORF78 partially localizes to centromeres and plays a role in chromosome segregation

C9ORF78 partially localizes to centromeres and plays a role in chromosome segregation

  • Exp Cell Res. 2022 Apr 15;413(2):113063. doi: 10.1016/j.yexcr.2022.113063.
Radhika Koranne 1,  Kayla Brown 1,  Hannah Vandenbroek 1,  William R Taylor 2
Affiliations

Affiliations

  • 1 Department of Biological Sciences, University of Toledo, 2801 W. Bancroft Street, MS 601, Toledo, OH, 43606, USA.
  • 2 Department of Biological Sciences, University of Toledo, 2801 W. Bancroft Street, MS 601, Toledo, OH, 43606, USA. Electronic address: [email protected].
PMID: 35167828 DOI: 10.1016/j.yexcr.2022.113063
Abstract

C9ORF78 is a poorly characterized protein found in diverse eukaryotes. Previous work indicated overexpression of C9ORF78 in malignant tissues indicating a possible involvement in growth regulatory pathways. Additional studies in fission yeast and humans uncover a potential function in regulating the spliceosome. In studies of GFP-tagged C9ORF78 we observed a dramatic reduction in protein abundance in cells grown to confluence and/or deprived of serum growth factors. Serum stimulation induced synchronous re-expression of the protein in HeLa cells. This effect was also observed with the endogenous protein. Overexpressing either E2F1 or N-Myc resulted in elevated C9ORF78 expression potentially explaining the serum-dependent upregulation of the protein. Immunofluorescence analysis indicates that C9ORF78 localizes to nuclei in interphase but does not appear to concentrate in speckles as would be expected for a splicing protein. Surprisingly, a subpopulation of C9ORF78 co-localizes with ACA, Mad1 and Ndc80 in mitotic cells suggesting that this protein associates with kinetochores or centromeres. Levels of C9ORF78 at the centromere/kinetochore also increased upon activation of the mitotic checkpoint. Furthermore, knocking-down C9ORF78 caused mitotic defects. These studies uncover novel mitotic function and subcellular localization of C9ORF78.

Keywords

Centromere; Checkpoint; Kinetochore; Mitosis; Spliceosome.

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