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Aurora kinase B-phosphorylated HP1α functions in chromosomal instability. Cell Cycle 2019 Jun;18(12):1407-1421

Date

05/28/2019

Pubmed ID

31130069

Pubmed Central ID

PMC6592258

DOI

10.1080/15384101.2019.1618126

Scopus ID

2-s2.0-85067316375 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

Heterochromatin Protein 1 α (HP1α) associates with members of the chromosome passenger complex (CPC) during mitosis, at centromeres where it is required for full Aurora Kinase B (AURKB) activity. Conversely, recent reports have identified AURKB as the major kinase responsible for phosphorylation of HP1α at Serine 92 (S92) during mitosis. Thus, the current study was designed to better understand the functional role of this posttranslationally modified form of HP1α. We find that S92-phosphorylated HP1α is generated in cells at early prophase, localizes to centromeres, and associates with regulators of chromosome stability, such as Inner Centromere Protein, INCENP. In mouse embryonic fibroblasts, HP1α knockout alone or reconstituted with a non-phosphorylatable (S92A) HP1α mutant results in mitotic chromosomal instability characterized by the formation of anaphase/telophase chromatin bridges and micronuclei. These effects are rescued by exogenous expression of wild type HP1α or a phosphomimetic (S92D) variant. Thus, the results from the current study extend our knowledge of the role of HP1α in chromosomal stability during mitosis.

Author List

Williams MM, Mathison AJ, Christensen T, Greipp PT, Knutson DL, Klee EW, Zimmermann MT, Iovanna J, Lomberk GA, Urrutia RA

Authors

Gwen Lomberk PhD Professor in the Surgery department at Medical College of Wisconsin
Angela Mathison PhD Associate Professor in the Surgery department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin
Michael T. Zimmermann PhD Director, Associate Professor in the Data Science Institute department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Aurora Kinase B
Chromosomal Instability
Chromosomal Proteins, Non-Histone
Chromosome Aberrations
HeLa Cells
Heterochromatin
Humans
Kinetochores
Mice
Mice, Inbred C57BL
Mitosis
Phosphorylation
Phosphoserine
Protein Binding
Protein Kinase Inhibitors