DNA-PKcs inhibition impairs HDAC6-mediated HSP90 chaperone function on Aurora A and enhances HDACs inhibitor-induced cell killing by increasing mitotic aberrant spindle assembly

References

• Chan DW, Chen BP, Chen DJ, et al. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev. 2002;16(18):2333–2338.
   PubMed Web of Science ®Google Scholar
• Chen BP, Chan DW, Chen DJ, et al. Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks. J Biol Chem. 2005;280(15):14709–14715.
   PubMed Web of Science ®Google Scholar
• Chen BPC, Uematsu N, Chen DJ, et al. Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break. J Biol Chem. 2007;282(9):6582–6587.
   PubMed Web of Science ®Google Scholar
• Uematsu N, Weterings E, Chen DJ, et al. Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks. J Cell Biol. 2007;177(2):219–229.
   PubMed Web of Science ®Google Scholar
• Ding Q, Reddy YVR, Meek K, et al. Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair. Mol Cell Biol. 2003;23(16):5836–5848.
   PubMed Web of Science ®Google Scholar
• Merkle D, Douglas P, Lees-Miller SP, et al. The DNA-dependent protein kinase interacts with DNA to form a protein−DNA complex that is disrupted by phosphorylation. Biochemistry. 2002;41(42):12706–12714.
   PubMed Web of Science ®Google Scholar
• Calsou P, Frit P, Salles B, et al. The DNA-dependent protein kinase catalytic activity regulates DNA end processing by means of Ku entry into DNA. J Biol Chem. 1999;274(12):7848–7856.
   PubMed Web of Science ®Google Scholar
• Yajima H, Lee KJ, Chen BPC. ATR-dependent phosphorylation of DNA-dependent protein kinase catalytic subunit in response to UV-induced replication stress. Mol Cell Biol. 2006;26(7520–7528):7520–7528.
   PubMedGoogle Scholar
• Lin YF, Shih HY, Chen BPC, et al. PIDD mediates the association of DNA-PKcs and ATR at stalled replication forks to facilitate the ATR signaling pathway. Nucleic Acids Res. 2018;46(4):1847–1859.
   PubMed Web of Science ®Google Scholar
• Douglas P, Ye RQ, Lees-Miller SP, et al. Polo-like kinase 1 (PLK1) and protein phosphatase 6 (PP6) regulate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation in mitosis. Biosci Rep. 2014;34(3):e00113.
   PubMedGoogle Scholar
• Lee KJ, Lin YF, Chen BPC, et al. Involvement of DNA-dependent protein kinase in normal cell cycle progression through mitosis. J Biol Chem. 2011;286(14):12796–12802.
   PubMed Web of Science ®Google Scholar
• Shang Z, Yu L, Chen BPC, et al. DNA-PKcs activates the Chk2-Brca1 pathway during mitosis to ensure chromosomal stability. Oncogenesis. 2014;3(2):e85.
   PubMedGoogle Scholar
• Lee KJ, Shang ZF, Chen BPC, et al. The catalytic subunit of DNA-dependent protein kinase coordinates with polo-like kinase 1 to facilitate mitotic entry. Neoplasia. 2015;17(4):329–338.
   PubMed Web of Science ®Google Scholar
• Carey N, La Thangue NB. Histone deacetylase inhibitors: gathering pace. Curr Opin Pharmacol. 2006;6(4):369–375.
   PubMed Web of Science ®Google Scholar
• Marks PA, Rifkind RA, Kelly WK, et al. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 2001;1(3):194–202.
   PubMed Web of Science ®Google Scholar
• Dong L, Dong Q, Kung HF, et al. Novel HDAC5-interacting motifs of Tbx3 are essential for the suppression of E-cadherin expression and for the promotion of metastasis in hepatocellular carcinoma. Signal Transduct Target Ther. 2018;3:22.
   PubMed Web of Science ®Google Scholar
• Cimini D, Mattiuzzo M, Degrassi F, et al. Histone hyperacetylation in mitosis prevents sister chromatid separation and produces chromosome segregation defects. Mol Biol Cell. 2003;14(9):3821–3833.
   PubMed Web of Science ®Google Scholar
• Ma Y, Cai S, Zhang C, et al. Inhibition of protein deacetylation by trichostatin A impairs microtubule-kinetochore attachment. Cell Mol Life Sci. 2008;65(19):3100–3109.
   PubMed Web of Science ®Google Scholar
• Taddei A, Roche D, Almouzni G, et al. The effects of histone deacetylase inhibitors on heterochromatin: implications for anticancer therapy? EMBO Rep. 2005;6(6):520–524.
   PubMed Web of Science ®Google Scholar
• Li Y, Kao GD, Lazar MA, et al. A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity. Genes Dev. 2006;20(18):2566–2579.
   PubMed Web of Science ®Google Scholar
• Foley EA, Kapoor TM. Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat Rev Mol Cell Bio. 2013;14(1):25–37.
   PubMed Web of Science ®Google Scholar
• Stevens FE, Beamish H, Gabrielli B, et al. Histone deacetylase inhibitors induce mitotic slippage. Oncogene. 2008;27(10):1345–1354.
   PubMed Web of Science ®Google Scholar
• Magnaghi-Jaulin L, Eot-Houllier G, Jaulin C, et al. Histone deacetylase inhibitors induce premature sister chromatid separation and override the mitotic spindle assembly checkpoint. Cancer Res. 2007;67(13):6360–6367.
   PubMed Web of Science ®Google Scholar
• Park JH, Jong HS, Kim TY, et al. Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase. J Mol Med. 2008;86(1):117–128.
   PubMed Web of Science ®Google Scholar
• de Carcer G. Heat shock protein 90 regulates the metaphase-anaphase transition in a polo-like kinase-dependent manner. Cancer Res. 2004;64(15):5106–5112.
   PubMed Web of Science ®Google Scholar
• Wissing MD, Mendonca J, Kachhap SK, et al. Targeting prostate cancer cell lines with polo-like kinase 1 innibitors as a single agent and in combination with histone deacetylase inhibitors. Faseb J. 2013;27:4279–4293.
   PubMed Web of Science ®Google Scholar
• Kretzner L, Scuto A, Kirschbaum MH, et al. Combining histone deacetylase inhibitor vorinostat with Aurora kinase inhibitors enhances lymphoma cell killing with repression of c-Myc, hTERT, and microRNA levels. Cancer Res. 2011;71(11):3912–3920.
   PubMed Web of Science ®Google Scholar
• Dowling M, Voong KR, Kao GD, et al. Mitotic spindle checkpoint inactivation by trichostatin A defines a mechanism for increasing cancer cell killing by microtubule-disrupting agents. Cancer Biol Ther. 2005;4(2):197–206.
   PubMed Web of Science ®Google Scholar
• Ruis BL, Fattah KR, Hendrickson EA. The catalytic subunit of DNA-dependent protein kinase regulates proliferation, telomere length, and genomic stability in human somatic cells. Mol Cell Biol. 2008;28(20):6182–6195.
   PubMed Web of Science ®Google Scholar
• Peng YL, Zhang QM, Bedford JS, et al. Silencing expression of the catalytic subunit of DNA-dependent protein kinase by small interfering RNA sensitizes human cells for radiation-induced chromosome damage, cell killing, and mutation. Cancer Res. 2002;62(22):6400–6404.
   PubMed Web of Science ®Google Scholar
• Li M, Gu MM, Shang ZF, et al. The vanillin derivative VND3207 protects intestine against radiation injury by modulating p53/NOXA signaling pathway and restoring the balance of gut microbiota. Free Radical Bio Med. 2019;145:223–226.
   PubMed Web of Science ®Google Scholar
• Zhang ZH, Yamashita H, Iwase H, et al. HDAC6 expression is correlated with better survival in breast cancer. Clin Cancer Res. 2004;10(20):6962–6968.
   PubMed Web of Science ®Google Scholar
• Yan J, Seibenhener ML, Wooten MC, et al. SQSTM1/p62 interacts with HDAC6 and regulates deacetylase activity. PLoS One. 2013;8(9):e76016.
   PubMed Web of Science ®Google Scholar
• Lee JH, Choy ML, Marks PA, et al. Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair. Proc Natl Acad Sci U S A. 2010;107(33):14639–14644.
   PubMed Web of Science ®Google Scholar
• Robert C, Rassool FV. HDAC inhibitors: roles of DNA damage and repair. Adv Cancer Res. 2012;116:87–129.
   PubMed Web of Science ®Google Scholar
• Liu Q, Ruderman JV. Aurora A, mitotic entry, and spindle bipolarity. Proc Natl Acad Sci U S A. 2006;103(15):5811–5816.
   PubMed Web of Science ®Google Scholar
• Schopf FH, Biebl MM, Buchner J. The HSP90 chaperone machinery. Nat Rev Mol Cell Bio. 2017;18(6):345–360.
   PubMed Web of Science ®Google Scholar
• Kramer OH, Mahboobi S, Sellmer A. Drugging the HDAC6-HSP90 interplay in malignant cells. Trends Pharmacol Sci. 2014;35(10):501–509.
   PubMed Web of Science ®Google Scholar
• Cowley DO, Rivera-Perez JA, Van Dyke T, et al. Aurora-A kinase is essential for bipolar spindle formation and early development. Mol Cell Biol. 2009;29(4):1059–1071.
   PubMed Web of Science ®Google Scholar
• Solier S, Kohn KW, Pommier Y, et al. Heat shock protein 90 alpha (HSP90 alpha), a substrate and chaperone of DNA-PK necessary for the apoptotic response. Proc Natl Acad Sci U S A. 2012;109(32):12866–12872.
   PubMed Web of Science ®Google Scholar
• Quanz M, Herbette A, Dutreix M, et al. Heat shock protein 90 alpha (Hsp90 alpha) is phosphorylated in response to DNA damage and accumulates in repair foci. J Biol Chem. 2012;287(12):8803–8815.
   PubMed Web of Science ®Google Scholar
• Ding G, Liu HD, Huang G, et al. HDAC6 promotes hepatocellular carcinoma progression by inhibiting P53 transcriptional activity. FEBS Lett. 2013;587(7):880–886.
   PubMed Web of Science ®Google Scholar
• Liu L, Kwak YT, Gaynor RB, et al. DNA-dependent protein kinase phosphorylation of I kappa B beta and I kappa B beta regulates NF-kappa B DNA binding properties. Mol Cell Biol. 1998;18(7):4221–4234.
   PubMed Web of Science ®Google Scholar
• Li MX, Lin YF, Chen BPC, et al. The catalytic subunit of DNA-dependent protein kinase is required for cellular resistance to oxidative stress independent of DNA double-strand break repair. Free Radical Bio Med. 2014;76:278–285.
   PubMed Web of Science ®Google Scholar
• Song ZQ, Xie Y, Zhou PK, et al. Genome-wide identification of DNA-PKcs-associated RNAs by RIP-Seq. Signal Transduct Target Ther. 2019;4(1):22.
   PubMedGoogle Scholar
• Zhang M, Xiang SY, Wang CG, et al. HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutS alpha. Mol Cell. 2014;55(1):31–46.
   PubMed Web of Science ®Google Scholar
• Zhou J, Vos CC, Giannakakou P, et al. The protein farnesyltransferase regulates HDAC6 activity in a microtubule-dependent manner. J Biol Chem. 2009;284(15):9648–9655.
   PubMed Web of Science ®Google Scholar
• Wickstrom SA, Masoumi KC, Massoumi R, et al. CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin. Embo J. 2010;29(1):131–144.
   PubMed Web of Science ®Google Scholar
• Williams KA, Zhang M, Fang B, et al. Extracellular signal-regulated kinase (ERK) phosphorylates histone deacetylase 6 (HDAC6) at serine 1035 to stimulate cell migration. J Biol Chem. 2013;288(46):33156–33170.
   PubMed Web of Science ®Google Scholar
• Chen SG, Owens GC, Edelman DB, et al. HDAC6 regulates mitochondrial transport in hippocampal neurons. PLoS One. 2010;5(5):e10848.
   PubMed Web of Science ®Google Scholar
• Deribe YL, Wild P, Fetchko MJ, et al. Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Sci Signal. 2009;2(102):ra84.
   PubMed Web of Science ®Google Scholar
• Hsu FM, Zhang SC, Chen BPC. Role of DNA-dependent protein kinase catalytic subunit in cancer development and treatment. Transl Cancer Res. 2012;1(1):22–34.
   PubMed Web of Science ®Google Scholar