HDAC9 regulates the alternative lengthening of telomere (ALT) pathway via the formation of ALT-associated PML bodies

Mohd Raeed Jamiruddin, Taku Kaitsuka, Farzana Hakim, Atsushi Fujimura, Fan Yan Wei, Hisato Saitoh, Kazuhito Tomizawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cancer cells overcome cellular senescence by activating the telomere maintenance mechanism, which can be either through telomerase or the alternative lengthening of telomeres (ALT). Being exclusive to cancer cells, targeting ALT is a more promising route for the development of drugs against cancer. The histone deacetylase (HDAC) family plays significant roles in various cellular processes. In addition to the regulation of gene expression, HDACs are also known to directly interact with many proteins. We focused on this family, and found that HDAC9 was up-regulated in ALT-positive cells. In ALT-positive cells treated with HDAC9 siRNA, there was a decrease in the telomere replicative capacity, which was evident from the C-circles assay. Furthermore, the formation of ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs) was inhibited by HDAC9 knockdown. Based on this study, it is suggested that HDAC9 regulates the formation of APBs and could be a candidate for the target of ALT-cancer therapy.

Original languageEnglish
Pages (from-to)25-30
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume481
Issue number1-2
DOIs
Publication statusPublished - Dec 2 2016
Externally publishedYes

Fingerprint

Telomere Homeostasis
Leukemia
Cells
Telomere
Histone Deacetylases
Telomerase
Neoplasms
Gene expression
Small Interfering RNA
Assays
Cell Aging
Gene Expression Regulation
Maintenance
Pharmaceutical Preparations
Proteins

Keywords

  • Alternative lengthening of telomere (ALT)
  • Cancer biology
  • Histone deacetylase (HDAC)
  • Histone deacetylase 9 (HDAC9)
  • Promyelocytic leukemia (PML)
  • Telomere

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

HDAC9 regulates the alternative lengthening of telomere (ALT) pathway via the formation of ALT-associated PML bodies. / Jamiruddin, Mohd Raeed; Kaitsuka, Taku; Hakim, Farzana; Fujimura, Atsushi; Wei, Fan Yan; Saitoh, Hisato; Tomizawa, Kazuhito.

In: Biochemical and Biophysical Research Communications, Vol. 481, No. 1-2, 02.12.2016, p. 25-30.

Research output: Contribution to journalArticle

Jamiruddin, Mohd Raeed ; Kaitsuka, Taku ; Hakim, Farzana ; Fujimura, Atsushi ; Wei, Fan Yan ; Saitoh, Hisato ; Tomizawa, Kazuhito. / HDAC9 regulates the alternative lengthening of telomere (ALT) pathway via the formation of ALT-associated PML bodies. In: Biochemical and Biophysical Research Communications. 2016 ; Vol. 481, No. 1-2. pp. 25-30.
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