Cleavage and Cytoplasmic Relocalization of Histone Deacetylase 3 Are Important for Apoptosis Progression

Escaffit, Fabrice; Vaute, Olivier; Chevillard-Briet, Martine; Ségui, Bruno; Yasuda, Takami; Nakayama, Tatsuo; Trouche, Didier

doi:10.1128/mcb.00869-06

Cited by 61 publications

(74 citation statements)

References 52 publications

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“…Recently, subcellular localization of HDAC3 was also shown to be controlled by caspase-dependent cleavage during apoptosis (Escaffit et al, 2007). Removal of the C-terminal part of HDAC3, which is required for nuclear localization, results in accumulation of the cleaved protein to the cytoplasm.…”

Section: Regulation Of Hdac3 Activitymentioning

confidence: 99%

“…Removal of the C-terminal part of HDAC3, which is required for nuclear localization, results in accumulation of the cleaved protein to the cytoplasm. The redistribution of HDAC3 is required for proapoptotic gene activation and subsequent death of several human cell types (Escaffit et al, 2007). Interestingly, the cleaved HDAC3 protein appears to maintain its deacetylase enzymatic activity, raising a possible cytoplasmic role for the cleaved HDAC3 (Escaffit et al, 2007).…”

Section: Regulation Of Hdac3 Activitymentioning

confidence: 99%

“…Finally, two recent publications illustrate a more specific implication of HDAC3 in apoptosis. The first study shows that cytoplasmic relocalization of cleaved HDAC3 to be critical for cell death (Escaffit et al, 2007), whereas the other demonstrates a transcriptional effect of HDAC3 on c-jun (Xia et al, 2007).…”

Section: Hdac3 As An Attractive Therapeutic Targetmentioning

confidence: 99%

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HDAC3: taking the SMRT-N-CoRrect road to repression

2007

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Known histone deacetylases (HDACs) are divided into different classes, and HDAC3 belongs to Class I. Through forming multiprotein complexes with the corepressors SMRT and N-CoR, HDAC3 regulates the transcription of a plethora of genes. A growing list of nonhistone substrates extends the role of HDAC3 beyond transcriptional repression. Here, we review data on the composition, regulation and mechanism of action of the SMRT/ N-CoR-HDAC3 complexes and provide several examples of nontranscriptional functions, to illustrate the wide variety of physiological processes affected by this deacetylase. Furthermore, we discuss the implication of HDAC3 in cancer, focusing on leukemia. We conclude with some thoughts about the potential therapeutic efficacies of HDAC3 activity modulation.

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Section: Regulation Of Hdac3 Activitymentioning

confidence: 99%

Section: Regulation Of Hdac3 Activitymentioning

confidence: 99%

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HDAC3: taking the SMRT-N-CoRrect road to repression

2007

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“…Colorectal cancer cell lines, control or overexpressing Tip60, were obtained using retroviral-mediated transfer as previously described (Escaffit et al, 2007) using pLPCX or pLPCX-Tip60 vectors. Puromycin (1 mg/ml; Invitrogen SARL) was added 48 h following infection and stable colorectal cancer R LPCX Empty or R LPCX Tip60 cell populations were obtained after 10 days of treatment.…”

Section: Generation Of Stable Cell Linesmentioning

confidence: 99%

“…Immunofluorescence of cells on coverslips, observations and acquisition of native images were performed as previously described (Escaffit et al, 2007). Quantification of fluorescence levels was done using home-developed macros in ImageJ software (National Institutes of Health, Bethesda, MA, USA) to normalize background, thresholds and measures.…”

Section: Dapi Staining Immunofluorescence and Quantificationmentioning

confidence: 99%

The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways

et al. 2009

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The Tip60 histone acetyltransferase belongs to a multimolecular complex that contains many chromatin remodeling enzymes including the ATPase p400, a protein involved in nucleosomal incorporation of specific histone variants and that can directly or indirectly repress some Tip60-dependent pathways. Tip60 activity is critical for the cellular response to DNA damage and is affected during cancer progression. Here, we found that the ratio between Tip60 and p400 mRNAs is affected in most colorectal carcinoma. Strikingly, reversing the p400/ Tip60 imbalance by Tip60 overexpression or the use of siRNAs resulted in increased apoptosis and decreased proliferation of colon-cancer-derived cells, suggesting that this ratio defect is important for cancer progression. Furthermore, we demonstrate that the p400/Tip60 ratio controls the oncogene-induced DNA damage response, a known anticancer barrier. Finally, we found that it is also critical for the response to 5-fluorouracil, a first-line treatment against colon cancer. Together, our data indicate that the p400/Tip60 ratio is critical for colon cancer cells proliferation and response to therapeutic drugs through the control of stress-response pathways.

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Effect of the histone deacetylase inhibitor SNDX‐275 on Fas signaling in osteosarcoma cells and the feasibility of its topical application for the treatment of osteosarcoma lung metastases

Koshkina

Rao-Bindal

Kleinerman

2011

Cancer

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BACKGROUND:Patients with lung metastases from osteosarcoma (OS) have poor response to salvage therapy. Understanding the mechanisms involved in the metastatic process of OS may lead to new effective therapeutic approaches. The authors reported previously that up-regulation of the Fas receptor by transfecting OS cells with Fas plasmid inhibited the in vivo growth of metastases in the lungs. METHODS: In the current study, the authors treated OS cells with the histone deacetylase inhibitor SNDX-275 and studied its cytotoxicity and its effect on Fas signaling in vitro and in vivo. RESULTS: Subtoxic doses of SNDX-275 were able to activate the Fas pathway in OS cells by increasing the expression of Fas messenger RNA; however, the increased expression was not always followed by increased levels of Fas receptor expression on the cell surface. The treatment of cells with a combination of SNDX-275 and Fas ligand (FasL) had a stronger cytotoxic effect on tested OS cells than either agent alone. Inhibition of the Fas pathway in cells by inhibition of the Fas-associated death domain (FADD) molecule eliminated this combination effect, indicating that activity of FADD is important for the efficacy of this agent in the FasL-expressing environment of the lungs. Intranasal administration of SNDX-275 in mice with OS lung metastases revealed that SNDX-275 may inhibit metastatic growth at a dose of 0.13 mg/kg, which is approximately 200-fold lower than the therapeutically effective oral dose reported previously. CONCLUSIONS: The current findings indicated that SNDX-275 can activate Fas signaling in OS cells in vitro and in vivo and that the administration of SDNX-275 by inhalation is feasible as a treatment for OS metastases and warrants its further investigation.

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Cleavage and Cytoplasmic Relocalization of Histone Deacetylase 3 Are Important for Apoptosis Progression

Cited by 61 publications

References 52 publications

HDAC3: taking the SMRT-N-CoRrect road to repression

HDAC3: taking the SMRT-N-CoRrect road to repression

The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways

Effect of the histone deacetylase inhibitor SNDX‐275 on Fas signaling in osteosarcoma cells and the feasibility of its topical application for the treatment of osteosarcoma lung metastases

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