Gene interactions and pathways from curated databases and text-mining

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CDKN1A — HDAC1

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Xiao et al., J Cell Biochem 1999 : Both Sp1 and Sp3 are responsible for p21waf1 promoter activity induced by histone deacetylase inhibitor in NIH3T3 cells
Sowa et al., Cancer Res 1999 : Sp3, but not Sp1, mediates the transcriptional activation of the p21/WAF1/Cip1 gene promoter by histone deacetylase inhibitor
Xiao et al., J Biol Chem 2000 : p300 collaborates with Sp1 and Sp3 in p21 ( waf1/cip1 ) promoter activation induced by histone deacetylase inhibitor
Shin et al., Cancer Res 2000 (Stomach Neoplasms) : The p21 gene was activated only by histone deacetylase inhibitor
Claassen et al., Proc Natl Acad Sci U S A 2000 : Repression of p21 ( CIP1 ) transcription by c-Myc occurred at the promoter level in a region near the start site of transcriptional initiation and was independent of histone deacetylase activity
Suzuki et al., Int J Cancer 2000 (Mouth Neoplasms...) : TSA enhanced the protein expression of p21 ( WAF1 ), CREB binding protein, cyclinE, cyclin A, Bak and Bax, while it reduced the expression of E2F-1, E2F-4, HDAC1 , p53 and hyperphosphorylated form of Rb
Huang et al., Oncogene 2000 (Breast Neoplasms) : Activation of the p21WAF1/CIP1 promoter independent of p53 by the histone deacetylase inhibitor suberoylanilide hydroxamic acid ( SAHA ) through the Sp1 sites
Sowa et al., Biofactors 2000 (Colorectal Neoplasms...) : As a model of this, we found that histone deacetylase inhibitors such as butyrate or trichostatin A dramatically stimulate the p21/WAF1 gene promoter through the Spl sites, resulting in cell cycle arrest
Han et al., J Biol Chem 2001 : Activation of p21 ( WAF1/Cip1 ) transcription through Sp1 sites by histone deacetylase inhibitor apicidin : involvement of protein kinase C
Burgess et al., Mol Pharmacol 2001 : Up-regulation of p21 ( WAF1/CIP1 ) by histone deacetylase inhibitors reduces their cytotoxicity
Imanishi et al., J Clin Endocrinol Metab 2002 (Thyroid Neoplasms) : Western blot analysis demonstrated that the HDAC-1 increased the expression of acetylated histones, as well as of p21 ( cip1/waf1 ), but did not affect levels of total histone and endogenous p53
Blagosklonny et al., Mol Cancer Ther 2002 : By preventing deacetylation of histones, histone deacetylase inhibitors ( HDIs ) transcriptionally induce p21
Lagger et al., Mol Cell Biol 2003 : Our findings show that the deacetylase HDAC1 acts as an antagonist of the tumor suppressor p53 in the regulation of the cyclin dependent kinase inhibitor p21 and provide a basis for understanding the function of histone deacetylase inhibitors as antitumor drugs
Ju et al., Cancer Res 2003 (Ataxia Telangiectasia) : In this work, we show that p21 ( WAF1 ) induction by HDAC inhibitors ( depsipeptide and trichostatin A ) is defective in Ataxia telangiectasia ( AT ) cells but normal in matched wild-type ( WT ) cells ( human diploid fibroblasts ) ... To verify the role of ATM in this effect, we show that ectopic expression of the WT ATM gene in an AT cell line fully restores p21 ( WAF1 ) induction by the HDAC inhibitors
Sowa et al., Nihon Eiseigaku Zasshi 2003 (Neoplasms) : As a model of our hypothesis, we found that histone deacetylase inhibitors such as butyrate and trichostatin A dramatically stimulate the p21/WAF1 gene promoter through the Sp1 sites, resulting in cell cycle arrest
Davie et al., J Nutr 2003 (Breast Neoplasms) : A model is proposed in which inhibition of Sp1/Sp3 associated HDAC activity leads to histone hyperacetylation and transcriptional activation of the p21 ( Waf1/Cip1 ) gene ; p21 ( Waf1/Cip1 ) inhibits cyclin dependent kinase 2 activity and thereby arrests cell cycling
Barnes et al., Nat Struct Biol 2003 : We describe here the binding, phosphorylation and functional regulation of CtBP by the p21 activated kinase 1 (Pak1)
Donadelli et al., Mol Carcinog 2003 (Adenocarcinoma...) : In cells with an altered p53 gene, the expression of p21 ( WAF1/CIP1 ), a potent inhibitor of cyclin dependent kinases, can be induced by histone deacetylase (HDAC) inhibitors via a p53 independent pathway, which may play a critical role in arrest of cell growth
Chung et al., Mol Ther 2003 (Arthritis, Rheumatoid...) : We found that the histone deacetylase (HDAC) inhibitors ( phenylbutyrate and trichostatin A ) causing histone hyperacetylation to modulate multiple gene expression not only induced the expression of p21 ( Cip1 ) and p16(INK4) in synovial cells but also inhibited the expression of tumor necrosis factor-alpha in affected tissues in adjuvant arthritis, an animal model of RA
Gui et al., Proc Natl Acad Sci U S A 2004 : Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter associated proteins, including HDAC1
Piekarz et al., Blood 2004 (Lymphoma, T-Cell) : Treatment with depsipeptide, as well as other histone deacetylase inhibitors, caused induction of histone acetylation, induction of p21 expression, and substantial apoptosis without significant cell cycle arrest
Chen et al., Zhonghua Yi Xue Za Zhi 2004 (Colonic Neoplasms) : In these two human colon cancer cell lines, HDAC inhibitors stimulate the p21 ( WAF1 ) gene expression by selectively increasing the degree of acetylation of the gene associated histones, and induce a G ( 1 ) cell cycle arrest
Li et al., Biochem Biophys Res Commun 2004 (Uterine Cervical Neoplasms) : However, the exact mechanism by which HDAC inhibitors induce p21WAF1/CIP1 remains unclear
Varshochi et al., J Biol Chem 2005 (Breast Neoplasms) : Co-immunoprecipitation, DNA `` pull-down, '' and chromatin immunoprecipitation experiments together showed that in cycling cells, estrogen receptor alpha and histone deacetylase 1 (HDAC1) are recruited to the proximal Sp1 sites of the promoter to repress p21Waf1 expression ... The fact that p21Waf1 expression is normally repressed by HDAC activity in cycling cells is further demonstrated by the finding that p21Waf1 transcription can be induced by the silencing of HDACs with small interfering RNA or treatment with HDAC inhibitors
Rocchi et al., Oncol Rep 2005 (Neuroblastoma) : p21Waf1/Cip1 is a common target induced by short-chain fatty acid HDAC inhibitors ( valproic acid, tributyrin and sodium butyrate ) in neuroblastoma cells
Wang et al., Biol Pharm Bull 2005 : The activated human HDAC1 significantly induced the expression levels of mRNA for p53, PPAR-gamma and Bak and reduced the p21 expression level compared with the levels in control littermates
Myzak et al., FASEB J 2006 (Cell Transformation, Neoplastic...) : In mice treated with a single oral dose of 10 mumol SFN, there was significant inhibition of HDAC activity in the colonic mucosa after 6 h, and immunoblots revealed a concomitant increase in acetylated histones H3 and H4, which returned to control levels by 48 h. Longer-term treatment with SFN in the diet resulted in levels of acetylated histones and p21 ( WAF1 ) in the ileum, colon, prostate, and peripheral blood mononuclear cells that were elevated compared with controls
Zhao et al., Mol Cell Biol 2006 : Here we found that an inhibitor of HDAC , depsipeptide ( FR901228 ), but not trichostatin A (TSA), induces p21 ( Waf1/Cip1 ) expression through both p53 and Sp1/Sp3 pathways in A549 cells ( which retain wild-type p53 )
Ocker et al., Int J Biochem Cell Biol 2007 : Several studies have shown that HDAC inhibitors strongly activate the expression of the cyclin dependent kinase inhibitor p21 ( cip1/waf1 ) through ( i ) enhanced histone acetylation around the p21 ( cip1/waf1 ) promoter and ( ii ) the Sp1 sites on the p21 ( cip1/waf1 ) promoter releasing the repressor HDAC1 from its binding
Sun et al., Proc Natl Acad Sci U S A 2007 : Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced neural stem cell proliferation, suggesting that the TLX interacting HDACs play an important role in neural stem cell proliferation
Condorelli et al., Br J Pharmacol 2008 (Neuroblastoma) : Accordingly, HDAC inhibitor induced cell killing and p21/Waf1/Cip1 upregulation is impaired in p53i-cells
Chehl et al., HPB (Oxford) 2009 : Tq also increased p21 WAF1 expression, inhibited histone deacetylase (HDAC) activity, and induced histone hyperacetylation
Yamaguchi et al., Cancer Sci 2010 (Gallbladder Neoplasms) : In TGBC2TKB cells, the expression of EZH2 and HDAC1/2 were decreased by SAHA treatment, and p16(INK4a), E-cadherin, and p21were simultaneously activated ; however, no such findings were obtained in HGECs, suggesting that the effect of SAHA depends on the EZH2 mediated tumor suppressor loss
Zupkovitz et al., Mol Cell Biol 2010 (Cell Transformation, Viral) : The cyclin dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation ... We show here that HDAC1 reversibly regulates cellular proliferation and represses the cyclin dependent kinase inhibitor p21 in embryonic stem cells ... Chromatin immunoprecipitation assays demonstrate a direct regulation of the p21 gene by HDAC1 in mouse embryonic fibroblasts
Yamaguchi et al., Genes Dev 2010 : These results indicate that HDAC1 and HDAC2, by normally repressing the expression of p21 and p57, regulate the G1-to-S-phase transition of the cell cycle
Madison et al., Oncogene 2010 : PARP inhibition attenuated activation of p21 transcription by both p53 independent and p53 dependent processes, in a CtBP dependent manner
Simboeck et al., J Biol Chem 2010 (MAP Kinase Signaling System) : Taken together we have revealed a cross-talk of reversible phosphorylation and acetylation signals that controls the activation of p21 by HDAC inhibitors and identify the phosphatase PP2A as chromatin associated transcriptional repressor in mammalian cells
Clarke et al., Mol Nutr Food Res 2011 (Hyperplasia...) : SFN treatment also selectively decreased HDAC activity, and Class I and II HDAC proteins, increased acetylated histone H3 at the promoter for P21, induced p21 expression and increased tubulin acetylation in prostate cancer cells
Matsuzaki et al., Environ Health Prev Med 2003 : Previously, we demonstrated that HDAC inhibitors, such as sodium butyrate and trichostatin A (TSA), transcriptionally induce the cyclin dependent kinase inhibitor p21 ( WAF1/Cip1 ), a downstream target gene of p53, in a p53 independent manner
Bellucci et al., PloS one 2013 (Breast Neoplasms) : Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z
Sachweh et al., Cell death & disease 2013 : Incompatible effects of p53 and HDAC inhibition on p21 expression and cell cycle progression
Dong et al., Journal of hematology & oncology 2013 : Molecular silencing of HDAC1 using small interfering RNA ( siRNA ) attenuated VPA mediated regulation of CDKN1A , CDKN1B and LC3-I/II, regression of tumor cell growth and induction of autophagy