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Role for histone deacetylase 1 in human tumor cell proliferation.
Senese S
,
Zaragoza K
,
Minardi S
,
Muradore I
,
Ronzoni S
,
Passafaro A
,
Bernard L
,
Draetta GF
,
Alcalay M
,
Seiser C
,
Chiocca S
.
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Posttranslational modifications of core histones are central to the regulation of gene expression. Histone deacetylases (HDACs) repress transcription by deacetylating histones, and class I HDACs have a crucial role in mouse, Xenopus laevis, zebra fish, and Caenorhabditis elegans development. The role of individual class I HDACs in tumor cell proliferation was investigated using RNA interference-mediated protein knockdown. We show here that in the absence of HDAC1 cells can arrest either at the G(1) phase of the cell cycle or at the G(2)/M transition, resulting in the loss of mitotic cells, cell growth inhibition, and an increase in the percentage of apoptotic cells. On the contrary, HDAC2 knockdown showed no effect on cell proliferation unless we concurrently knocked down HDAC1. Using gene expression profiling analysis, we found that inactivation of HDAC1 affected the transcription of specific target genes involved in proliferation and apoptosis. Furthermore, HDAC2 downregulation did not cause significant changes compared to control cells, while inactivation of HDAC1, HDAC1 plus HDAC2, or HDAC3 resulted in more distinct clusters. Loss of these HDACs might impair cell cycle progression by affecting not only the transcription of specific target genes but also other biological processes. Our data support the idea that a drug targeting specific HDACs could be highly beneficial in the treatment of cancer.
Ahringer,
NuRD and SIN3 histone deacetylase complexes in development.
2000, Pubmed
Ahringer,
NuRD and SIN3 histone deacetylase complexes in development.
2000,
Pubmed
Alcalay,
Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair.
2003,
Pubmed
Bartl,
Identification of mouse histone deacetylase 1 as a growth factor-inducible gene.
1997,
Pubmed
Bolden,
Anticancer activities of histone deacetylase inhibitors.
2006,
Pubmed
Choi,
Expression profile of histone deacetylase 1 in gastric cancer tissues.
2001,
Pubmed
Cobb,
Meiotic events at the centromeric heterochromatin: histone H3 phosphorylation, topoisomerase II alpha localization and chromosome condensation.
1999,
Pubmed
Cress,
Histone deacetylases, transcriptional control, and cancer.
2000,
Pubmed
David,
mSin3-associated protein, mSds3, is essential for pericentric heterochromatin formation and chromosome segregation in mammalian cells.
2003,
Pubmed
Ekwall,
Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres.
1997,
Pubmed
Finocchiaro,
GenePicker: replicate analysis of Affymetrix gene expression microarrays.
2004,
Pubmed
Fischle,
Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR.
2002,
Pubmed
Gao,
Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family.
2002,
Pubmed
Glaser,
Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines.
2003,
Pubmed
Glaser,
Role of class I and class II histone deacetylases in carcinoma cells using siRNA.
2003,
Pubmed
Gregoretti,
Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis.
2004,
Pubmed
Grozinger,
Deacetylase enzymes: biological functions and the use of small-molecule inhibitors.
2002,
Pubmed
Gurley,
Histone phosphorylation in late interphase and mitosis.
1973,
Pubmed
Halkidou,
Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer.
2004,
Pubmed
Hauser,
Activation of the mouse histone deacetylase 1 gene by cooperative histone phosphorylation and acetylation.
2002,
Pubmed
Henderson,
Role of caspases, Bid, and p53 in the apoptotic response triggered by histone deacetylase inhibitors trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA).
2003,
Pubmed
Henderson,
Apoptotic pathways activated by histone deacetylase inhibitors: implications for the drug-resistant phenotype.
2003,
Pubmed
Hendzel,
Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation.
1997,
Pubmed
Hsu,
Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes.
2000,
Pubmed
Huang,
Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1.
2005,
Pubmed
Hubbert,
HDAC6 is a microtubule-associated deacetylase.
2002,
Pubmed
Humphrey,
Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1.
2001,
Pubmed
Hutchins,
Many fingers on the mitotic trigger: post-translational regulation of the Cdc25C phosphatase.
2004,
Pubmed
,
Xenbase
Ito,
MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation.
2002,
Pubmed
Johnstone,
Histone-deacetylase inhibitors: novel drugs for the treatment of cancer.
2002,
Pubmed
Johnstone,
Histone deacetylase inhibitors in cancer therapy: is transcription the primary target?
2003,
Pubmed
Kartmann,
Novel roles for mammalian septins: from vesicle trafficking to oncogenesis.
2001,
Pubmed
Kawai,
Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor alpha.
2003,
Pubmed
Khochbin,
Functional significance of histone deacetylase diversity.
2001,
Pubmed
Kim,
Downregulation of gelsolin and retinoic acid receptor beta expression in gastric cancer tissues through histone deacetylase 1.
2004,
Pubmed
Krämer,
The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2.
2003,
Pubmed
Lagger,
Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression.
2002,
Pubmed
Lagger,
The tumor suppressor p53 and histone deacetylase 1 are antagonistic regulators of the cyclin-dependent kinase inhibitor p21/WAF1/CIP1 gene.
2003,
Pubmed
Li,
A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity.
2006,
Pubmed
Luo,
Negative control of p53 by Sir2alpha promotes cell survival under stress.
2001,
Pubmed
Marks,
Discovery and development of SAHA as an anticancer agent.
2007,
Pubmed
Marks,
Histone deacetylases and cancer: causes and therapies.
2001,
Pubmed
Ng,
Histone deacetylases: silencers for hire.
2000,
Pubmed
Ono,
SEPTIN6, a human homologue to mouse Septin6, is fused to MLL in infant acute myeloid leukemia with complex chromosomal abnormalities involving 11q23 and Xq24.
2002,
Pubmed
Patra,
Histone deacetylase and DNA methyltransferase in human prostate cancer.
2001,
Pubmed
Paulson,
Phosphorylation of histones 1 and 3 and nonhistone high mobility group 14 by an endogenous kinase in HeLa metaphase chromosomes.
1982,
Pubmed
Peart,
Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors.
2005,
Pubmed
Richon,
Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation.
2000,
Pubmed
Richon,
Second generation hybrid polar compounds are potent inducers of transformed cell differentiation.
1996,
Pubmed
Sasaki,
Ligand-induced recruitment of a histone deacetylase in the negative-feedback regulation of the thyrotropin beta gene.
1999,
Pubmed
Taddei,
Reversible disruption of pericentric heterochromatin and centromere function by inhibiting deacetylases.
2001,
Pubmed
Vance,
Tbx2 is overexpressed and plays an important role in maintaining proliferation and suppression of senescence in melanomas.
2005,
Pubmed
Vaziri,
hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase.
2001,
Pubmed
Weiss,
p21Waf1/Cip1 as a therapeutic target in breast and other cancers.
2003,
Pubmed
Wilson,
Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer.
2006,
Pubmed
Xu,
Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects.
2005,
Pubmed
Yang,
Multisite protein modification and intramolecular signaling.
2005,
Pubmed
Zhang,
HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo.
2003,
Pubmed
Zhu,
Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis.
2004,
Pubmed