FAM190A deficiency creates a cell division defect

Kalpesh Patel, Francesca Scrimieri, Soma Ghosh, Jun Zhong, Min Sik Kim, Yunzhao R. Ren, Richard A. Morgan, Christine A. Iacobuzio-Donahue, Akhilesh Pandey, Scott E. Kern

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)296-303
Number of pages8
JournalAmerican Journal of Pathology
Volume183
Issue number1
DOIs
StatePublished - Jul 1 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Patel, K., Scrimieri, F., Ghosh, S., Zhong, J., Kim, M. S., Ren, Y. R., Morgan, R. A., Iacobuzio-Donahue, C. A., Pandey, A., & Kern, S. E. (2013). FAM190A deficiency creates a cell division defect. American Journal of Pathology, 183(1), 296-303. https://doi.org/10.1016/j.ajpath.2013.03.020