Inhibition of protein deacetylation by trichostatin A impairs microtubule-kinetochore attachment

Y. Ma, S. Cai, Q. Lu, X. Lu, Q. Jiang, Jia Zhou, C. Zhang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Inhibition of protein deacetylation arrests cells in mitosis, but the mechanism is unknown. To understand why inhibiting protein deacetylation causes cell cycle arrest, we treated HeLa cells beyond G1/S transition with trichostatin A (TSA), a potent protein deacetylase inhibitor, and found that the cells arrested at prometaphase with ectopic spindles and unaligned chromosomes. The hyper-acetylated cells encountered a serious microtubule (MT)-kinetochore attachment problem, although the kinetochores are intact at ultrastructural level. By immunofluorescence staining of kinetochore proteins, we found that the pericentromeric H3K9Me3-HP1 pathway was disrupted and that the CENP-A-dependent outer plate protein dynamics of kinetochores was greatly diminished by the drug treatment. The treatment also caused the loss of chromosome passenger complex (CPC), the proposed error checking system, from centromere and impaired the microtubule dynamics of the cells. Overall, we propose that deacetylation inhibition impairs MT-kinetochore attachment through disrupting the centromere function and altering the kinetochore composition and MT dynamics.

Original languageEnglish (US)
Pages (from-to)3100-3109
Number of pages10
JournalCellular and Molecular Life Sciences
Volume65
Issue number19
DOIs
StatePublished - Oct 2008
Externally publishedYes

Fingerprint

trichostatin A
Kinetochores
Microtubules
Proteins
Centromere
Chromosomes
Prometaphase
Cell Cycle Checkpoints
HeLa Cells
Mitosis
Fluorescent Antibody Technique
Staining and Labeling
Therapeutics

Keywords

  • Chromosome passenger complex
  • Deacetylase inhibitor
  • Kinetochore
  • Mitotic centromere-associated kinesin
  • Trichostatin A

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Inhibition of protein deacetylation by trichostatin A impairs microtubule-kinetochore attachment. / Ma, Y.; Cai, S.; Lu, Q.; Lu, X.; Jiang, Q.; Zhou, Jia; Zhang, C.

In: Cellular and Molecular Life Sciences, Vol. 65, No. 19, 10.2008, p. 3100-3109.

Research output: Contribution to journalArticle

Ma, Y. ; Cai, S. ; Lu, Q. ; Lu, X. ; Jiang, Q. ; Zhou, Jia ; Zhang, C. / Inhibition of protein deacetylation by trichostatin A impairs microtubule-kinetochore attachment. In: Cellular and Molecular Life Sciences. 2008 ; Vol. 65, No. 19. pp. 3100-3109.
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