HDAC9 regulates the alternative lengthening of telomere (ALT) pathway via the formation of ALT-associated PML bodies.
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.
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Mohd Raeed
MR
Jamiruddin
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Taku
T
Kaitsuka
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Farzana
F
Hakim
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Atsushi
A
Fujimura
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Fan-Yan
FY
Wei
Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 860-8555, Japan.
Hisato
H
Saitoh
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. Electronic address: tomikt@kumamoto-u.ac.jp.
Kazuhito
K
Tomizawa
D045744:Cell Line, Tumor; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D012097:Repressor Proteins / Q000378:metabolism*; D016615:Telomere / Q000473:pathology*; D059505:Telomere Homeostasis
D012097:Repressor Proteins; C486544:HDAC9 protein, human; D006655:Histone Deacetylases
Alternative lengthening of telomere (ALT); Cancer biology; Histone deacetylase (HDAC); Histone deacetylase 9 (HDAC9); Promyelocytic leukemia (PML); Telomere