CK1-mediated phosphorylation of FAM110A promotes its interaction with mitotic spindle and controls chromosomal

Cecilia Aquino Perez1, Monika Burocziova1, Gabriela Jenikova1

  • 1Cancer Cell Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.

EMBO Reports
|June 3, 2021
PubMed

Insights

Family with sequence similarity 110 member A (FAM110A) regulates cell division by interacting with casein kinase I (CK1). CK1 phosphorylation of FAM110A is crucial for proper chromosomal alignment and mitotic spindle function during cell cycle progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Cell cycle progression is regulated by cyclin-dependent kinases, controlling key events like gene expression and cell division.
  • Identifying novel regulators of the cell cycle is crucial for understanding cell biology and disease.

Purpose of the Study:

  • To identify novel regulators of the cell cycle.
  • To investigate the role of Family with sequence similarity 110 member A (FAM110A) in cell division.
  • To elucidate the interaction between FAM110A and casein kinase I (CK1) during mitosis.

Main Methods:

  • Transcriptomic analysis of human cells using a fluorescent ubiquitination-based cell cycle indicator.
  • Mass spectrometry and immunoprecipitation to identify protein complexes.
  • In vitro kinase assays and site-directed mutagenesis to study protein phosphorylation.
  • Depletion studies using siRNA to assess protein function.

Main Results:

  • Identified 701 differentially expressed transcripts in G1 and G2 cells, including FAM110A, which is highly expressed in G2.
  • FAM110A localizes to the mitotic spindle and poles, and its depletion impairs chromosomal alignment and delays cell division.
  • Identified CK1 as a binding partner of FAM110A during mitosis.
  • CK1 phosphorylates FAM110A, and this phosphorylation is essential for FAM110A's function in chromosomal alignment and spindle orientation.

Conclusions:

  • FAM110A is a novel regulator of the cell cycle, essential for proper mitosis.
  • CK1-mediated phosphorylation of FAM110A is a critical mechanism for regulating chromosomal alignment and spindle function.
  • FAM110A interacts with the mitotic spindle, and its phosphorylation by CK1 promotes this interaction, ensuring accurate cell division.

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