title: FAM190A deficiency creates a cell division defect.
abstract: Like the p16, SMAD4, and RB1 genes, FAM190A (alias CCSER1) lies at a consensus site of homogeneous genomic deletions in human cancer. FAM190A transcripts in 40% of cancers also contain in-frame deletions of evolutionarily conserved exons. Its gene function was unknown. We found an internal deletion of the FAM190A gene in a pancreatic cancer having prominent focal multinuclearity. The experimental knockdown of FAM190A expression by shRNA caused focal cytokinesis defects, multipolar mitosis, and multinuclearity as observed in time-lapse microscopy. FAM190A was localized to the γ-tubulin ring complex of early mitosis and to the midbody in late cytokinesis by immunofluorescence assay and was present in the nuclear fraction of unsynchronized cells by immunoblot. FAM190A interacted with EXOC1 and Ndel1, which function in cytoskeletal organization and the cell division cycle. Levels of FAM190A protein peaked 12 hours after release from thymidine block, corresponding to M-phase. Slower-migrating phosphorylated forms accumulated toward M-phase and disappeared after release from a mitotic block and before cytokinesis. Studies of FAM190A alterations may provide mechanistic insights into mitotic dysregulation and multinuclearity in cancer. We propose that FAM190A is a regulator or structural component required for normal mitosis and that both the rare truncating mutations and common in-frame deletion alteration of FAM190A may contribute to the chromosomal instability of cancer.
authors.affiliation: Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
authors.forename: Kalpesh
authors.initials: K
authors.lastname: Patel
authors.forename: Francesca
authors.initials: F
authors.lastname: Scrimieri
authors.forename: Soma
authors.initials: S
authors.lastname: Ghosh
authors.forename: Jun
authors.initials: J
authors.lastname: Zhong
authors.forename: Min-Sik
authors.initials: MS
authors.lastname: Kim
authors.forename: Yunzhao R
authors.initials: YR
authors.lastname: Ren
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morgan
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kern
mesh_terms: D014408:Biomarkers, Tumor / Q000172:deficiency* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000172:deficiency* / Q000235:genetics; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D043171:Chromosomal Instability; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C583943:CCSER1 protein, human; D018797:Cell Cycle Proteins