Histone deacetylase 2 controls p53 and is a critical factor in tumorigenesis

Wagner, Tobias; Brand, P. W. J. L.; Heinzel, Thorsten; Krämer, Oliver H.

doi:10.1016/j.bbcan.2014.07.010

Cited by 60 publications

(72 citation statements)

References 202 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is also a considerable overlap in nuclear deacetylating activities. For example, the tumor suppressor p53 can be deacetylated by SIRT1, HDAC1, HDAC2 and HDAC3 (Luo et al, 2001;Vaziri et al, 2001;Juan et al, 2000;Ito et al, 2002;Wagner et al, 2014), and histone H4 lysine 16 is deacetylated by both SIRT1, SIRT2 and HDAC2 (Vaquero et al, 2004(Vaquero et al, , 2006Ma and Schultz, 2013). That is, there is a redundancy of NAD-dependent and -independent deacetylating enzymes for a variety of acetylated sites.…”

Section: Introductionmentioning

confidence: 99%

SIRT2 inactivation reveals a subset of hyperacetylated perinuclear microtubules inaccessible to HDAC6

Skoge

Ziegler

2016

Journal of Cell Science

View full text Add to dashboard Cite

Deacetylation of α-tubulin at lysine 40 is catalyzed by two enzymes, the NAD-dependent deacetylase SIRT2 and the NAD-independent deacetylase HDAC6, in apparently redundant reactions. In the present study, we tested whether these two enzymes might have distinguishable preferences for the deacetylation of different microtubule structures. Using various agents, we induced tubulin hyperacetylation and analyzed the ensuing formation of distinct microtubule structures. HDAC6 inhibition led to general hyperacetylation of the microtubule network throughout the cell, whereas hyperacetylation induced by SIRT2 inactivation was limited to perinuclear microtubules. Hyperacetylation of these perinuclear microtubules was undiminished following HDAC6 overexpression, whereas reactivation of SIRT2 restored the basal acetylation level and a normal microtubule network. By contrast, SIRT2 and HDAC6 acted similarly on the morphologically different, hyperacetylated microtubule structures induced by taxol, MAP2c overexpression or hyperosmotic stress. These results indicate overlapping and distinct functions of HDAC6 and SIRT2. We propose that the differential activity of the two deacetylases, which target the same acetylated lysine residue, might be related to the recognition of specific structural contexts.

show abstract

Section: Introductionmentioning

confidence: 99%

SIRT2 inactivation reveals a subset of hyperacetylated perinuclear microtubules inaccessible to HDAC6

Skoge

Ziegler

2016

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Class I histone deacetylases (HDAC) have been described to be elevated in gastric, breast, colorectal, lung, and liver cancers (17,18) and may contribute to those cancers' response to therapy. In melanoma, pan-HDAC inhibitors in combination with temozolomide have shown promise (19,20).…”

Section: Introductionmentioning

confidence: 99%

“…For these reasons, we addressed the role of class I HDACs in melanoma and determined the molecular mechanism whereby these HDACs influence the response of melanomas to temozolomide. The class I HDACs are HDAC1, HDAC2, HDAC3, and HDAC8 (17,18). They deacetylate histones and nonhistone proteins, thereby contributing to gene and protein regulation.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Histone Deacetylase Activity in Malignant Melanoma Provokes RAD51 and FANCD2-Triggered Drug Resistance

et al. 2016

View full text Add to dashboard Cite

DNA-damaging anticancer drugs remain a part of metastatic melanoma therapy. Epigenetic reprogramming caused by increased histone deacetylase (HDAC) activity arising during tumor formation may contribute to resistance of melanomas to the alkylating drugs temozolomide, dacarbazine, and fotemustine. Here, we report on the impact of class I HDACs on the response of malignant melanoma cells treated with alkylating agents. The data show that malignant melanomas in situ contain a high level of HDAC1/2 and malignant melanoma cells overexpress HDAC1/2/3 compared with noncancer cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes malignant melanoma cells to apoptosis following exposure to alkylating agents, while not affecting primary melanocytes. Inhibition of HDAC1/2/3 caused sensitization of melanoma cells to temozolomide in vitro and in melanoma xenografts in vivo. HDAC1/2/3 inhibition resulted in suppression of DNA double-strand break (DSB) repair by homologous recombination because of downregulation of RAD51 and FANCD2. This sensitized cells to the cytotoxic DNA lesion O 6 -methylguanine and caused a synthetic lethal interaction with the PARP-1 inhibitor olaparib. Furthermore, knockdown experiments identified HDAC2 as being responsible for the regulation of RAD51. The influence of class I HDACs on DSB repair by homologous recombination and the possible clinical implication on malignant melanoma therapy with temozolomide and other alkylating drugs suggests a combination approach where class I HDAC inhibitors such as valproic acid or MS-275 (entinostat) appear to counteract HDAC-and RAD51/FANCD2-mediated melanoma cell resistance. Cancer Res; 76(10); 3067-77. Ó2016 AACR.

show abstract

“…Deacetylases are frequently dysregulated in numerous tumors (7,8), Histone deacetylase 2 (HDAC2), an important member of type I histone deacetylases, plays a crucial role in tumor onset and development (8,9). Increasing evidence has revealed that HDAC2 is often overexpressed in various types of tumors (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

HDAC2 regulates cell proliferation, cell cycle progression and cell apoptosis in esophageal squamous cell carcinoma EC9706 cells

Wang

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract.Increasing evidence has demonstrated that histone deacetylase 2 (HDAC2) participates in the regulation of a variety of biological processes in numerous tumors. However, the potential role of HDAC2 in the development and progression of esophageal squamous cell carcinoma (ESCC) remains elusive. Immunohistochemistry was utilized to detect the expression of HDAC2, Cell Counting Kit-8 was used to determine the cell proliferation, and flow cytometry was employed to investigate cell cycle and cell apoptosis. Finally, western blotting was employed to detect the protein expression of cyclin D1, p21, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). The present study found that expression of HDAC2 protein in ESCC tissues was significantly increased compared with atypical hyperplasia tissues and normal esophageal mucosa (P<0.001). The expression of HDAC2 was not associated with the age or gender of patients (P>0.05), but was closely associated with the histological grade, invasion depth, tumor-node-metastasis stage and lymph node metastasis, respectively (all P<0.001). HDAC2 small interfering RNA effectively downregulated the expression of HDAC2 protein in ESCC EC9706 cells. Downregulation of HDAC2 expression evidently inhibited cell proliferation, arrested cell cycle at the G0/G1 phase and induced cell apoptosis in ESCC EC9706 cells, coupled with increased expression of p21 and Bax proteins and decreased expression of cyclin D1 and Bcl-2 proteins. Overall, the present findings suggest that HDAC2 may play an important role in the development and progression of ESCC and be considered as a novel molecular target for the treatment of ESCC.

show abstract

Histone deacetylase 2 controls p53 and is a critical factor in tumorigenesis

Cited by 60 publications

References 202 publications

SIRT2 inactivation reveals a subset of hyperacetylated perinuclear microtubules inaccessible to HDAC6

SIRT2 inactivation reveals a subset of hyperacetylated perinuclear microtubules inaccessible to HDAC6

Enhanced Histone Deacetylase Activity in Malignant Melanoma Provokes RAD51 and FANCD2-Triggered Drug Resistance

HDAC2 regulates cell proliferation, cell cycle progression and cell apoptosis in esophageal squamous cell carcinoma EC9706 cells

Contact Info

Product

Resources

About