TY - JOUR
T1 - HDAC9 regulates the alternative lengthening of telomere (ALT) pathway via the formation of ALT-associated PML bodies
AU - Jamiruddin, Mohd Raeed
AU - Kaitsuka, Taku
AU - Hakim, Farzana
AU - Fujimura, Atsushi
AU - Wei, Fan Yan
AU - Saitoh, Hisato
AU - Tomizawa, Kazuhito
N1 - Funding Information:
We thank A. Maeda for experimental support. This work was supported by a Grant-in-Aid for Young Scientists B (KAKENHI 15K18971 to T. K.) from the Japan Society for the Promotion of Science .
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/12/2
Y1 - 2016/12/2
N2 - 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.
AB - 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.
KW - Alternative lengthening of telomere (ALT)
KW - Cancer biology
KW - Histone deacetylase (HDAC)
KW - Histone deacetylase 9 (HDAC9)
KW - Promyelocytic leukemia (PML)
KW - Telomere
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U2 - 10.1016/j.bbrc.2016.11.026
DO - 10.1016/j.bbrc.2016.11.026
M3 - Article
C2 - 27833022
AN - SCOPUS:85001020537
SN - 0006-291X
VL - 481
SP - 25
EP - 30
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1-2
ER -
