JPOST Repositoryapplication/xmlhttps://storage.jpostdb.org/JPST002185/files/001_Control_500ng_T120_DDA_B4.wiff.scanhttps://storage.jpostdb.org/JPST002185/files/003_Fkbp_12h_500ng_T120_SW_B4.wiff.scanhttps://storage.jpostdb.org/JPST002185/files/003_Fkbp_12h_500ng_T120_DDA_B4.wiffhttps://storage.jpostdb.org/JPST002185/files/002_Fkbp_3h_500ng_T120_SW_B4.wiff.scanhttps://storage.jpostdb.org/JPST002185/files/002_Fkbp_3h_500ng_T120_DDA_B4.wiff.scanhttps://storage.jpostdb.org/JPST002185/files/002_Fkbp_3h_500ng_T120_DDA_B4.wiffhttps://storage.jpostdb.org/JPST002185/files/003_Fkbp_12h_500ng_T120_SW_B4.wiffhttps://storage.jpostdb.org/JPST002185/files/001_Control_500ng_T120_SW_B4.wiff.scanhttps://storage.jpostdb.org/JPST002185/files/003_Fkbp_12h_500ng_T120_DDA_B4.wiff.scanhttps://storage.jpostdb.org/JPST002185/files/001_Control_500ng_T120_SW_B4.wiffhttps://storage.jpostdb.org/JPST002185/files/001_Control_500ng_T120_DDA_B4.wiffhttps://storage.jpostdb.org/JPST002185/files/002_Fkbp_3h_500ng_T120_SW_B4.wiffhttps://storage.jpostdb.org/JPST002185/files/Control_Fkbp_500ng_T120_B4.groupprimaryOK200ProteomicsMidori ShimadaHomo Sapiens (human)https://repository.jpostdb.org/entry/JPST002185RIKENjPOSTExcess amounts of histones in the cell induce mitotic chromosome loss and genomic instability, and are therefore detrimental to cell survival. In yeast, excess histones are degraded by the proteasome mediated via the DNA damage response factor Rad53. Histone expression, therefore, is tightly regulated at the protein level. Our understanding of the transcriptional regulation of histone genes is far from complete. In this study, we found that calcineurin inhibitor treatment increased histone protein levels, and that the transcription factor NFATc1 (nuclear factor of activated T cells 1) repressed histone transcription and acts downstream of the calcineurin. We further revealed that NFATc1 binds to the promoter regions of many histone genes and that histone transcription is downregulated in a manner dependent on intracellular calcium levels. Indeed, overexpression of histone H3 markedly inhibited cell proliferation. Taken together, these findings suggest that NFATc1 prevents the detrimental effects of histone H3 accumulation by inhibiting expression of histone at the transcriptional level.Calcineurin/NFATc1 pathway represses cellular cytotoxicity by modulating histone H3 expression.Sato Yuki Y, Habara Makoto M, Hanaki Shunsuke S, Sharif Jafar J, Tomiyasu Haruki H, Miki Yosei Y, Shimada Midori MFK 506, Malignant Neoplasm, 18S*, 5R*, 1-c)(1, Neoplasms, 4)oxaazacyclotricosine-1, Anhydrous Tacrolimus, Benign Neoplasm, Prograft, Tumor, Prograf, Malignant, 19-dihydroxy-3-(2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl)-14, 10, 11, 12, 13, 14, Tacrolimus Anhydrous, 15, 16, 17, 18, MT, Benign, 19, 3S*, FR 900506, 9E, proteomic analysis, Neoplasm, Cell., 5, (3S-(3R*(E(1S*, 6, 7, 8, 20, 26a-hexadecahydro-5, 24, 25, 26, primary cancer, 4S*)), 19S*, 21(4H, Malignancy, 15S*, FR-900506, 26aR*))-, 23H)-tetrone, Benign Neoplasms, Cancers, FK-506, malignant tumor, Malignant Neoplasms, 16-dimethoxy-4, Neoplasias, 18-tetramethyl-8-(2-propenyl)-, 16R*, malignant neoplasm, monohydrate, 4S*, FK506, 14R*, 12R*, 8S*, Tacrolimus, Malignancies, Anhydrous, Neoplasia, 19-Epoxy-3H-pyrido(2, FR900506, Cancer, TumorsProtein Phosphatase 3 Regulatory Subunit, protein phosphatase type 2C activity, casein phosphatase, phosphatase IB, branched-chain alpha-keto acid dehydrogenase phosphatase, nf-atc, Phosphatase 3, phosphatase C-II, phosphatase II, protein D phosphatase, 3-hydroxy 3-methylglutaryl coenzymeA reductase phosphatase, nfat2, AI449492, phosphospectrin phosphatase, Histone, Protein Phosphatase 3, calna, Histone H2b, NF-ATc1, Histone H2a, protein phosphatase type 1 activity, Protein Phosphatase-2B, protein phosphatase type 2B, protein phosphatase type 2A, calna1, Protein, NFATc, BCKDH phosphatase, cna1, phosphatase H-II, HMG-CoA reductase phosphatase, Histone H3., intrinsic catalyst activity, phosphatase III, Histone H3.3, ppp2b, phosphatase 2A, phosphatase 2B, NFAT transcription complex cytosolic component, NFATc1, calcineurin, NFAT2, ccn1, caln, Nfatcb, NF-ATC, phosphatase SP, NFATC, protein phosphatase type 2B activity, serine/threonine specific protein phosphatase activity, Histone H1(s), calcium-dependent protein serine/threonine phosphatase, phosphopyruvate dehydrogenase phosphatase, protein phosphatase type 4 activity, 2210017P03Rik, phosphatase IV, Protein Phosphatase 2B, nfatc, Aspergillus awamori acid protein phosphatase, Calcineurin B, Calcineurin A, Histone H5, Histone H4, NF-ATc, Histone H7, protein phosphatase type 4, Protein Phosphatase 3 Catalytic Subunit, protein phosphatase type 1, protein phosphatase type 2A activity, polycation modulated (PCM-) phosphatase, protein phosphatase X, AV076380, Histone H1, phosphatase ITherapy, FK 506, 18S*, determination, Peptidomics, 5R*, 1-c)(1, 4)oxaazacyclotricosine-1, Anhydrous Tacrolimus, Proteins, Gene, Prograft, Prograf, 19-dihydroxy-3-(2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl)-14, Cell, 10, 11, 12, 13, 14, Tacrolimus Anhydrous, 15, 16, disease management., 17, 18, 19, 3S*, FR 900506, 9E, chemical analysis, Protein, Gene Products, 5, (3S-(3R*(E(1S*, 6, 7, 8, 20, 26a-hexadecahydro-5, treatment, 24, 25, 26, 4S*)), 19S*, Hs 578T, 21(4H, 15S*, FR-900506, HS578T, 26aR*))-, 23H)-tetrone, proteins, FK-506, Treatments, Protein Gene Products, 16-dimethoxy-4, Gene Proteins, 18-tetramethyl-8-(2-propenyl)-, Therapeutic, 16R*, monohydrate, 4S*, FK506, 14R*, 12R*, 8S*, Therapies, Treatment, Tacrolimus, assay, Anhydrous, 19-Epoxy-3H-pyrido(2, FR900506T-cell leukemia, Materials, nucleocytoplasm, mitotic chromosome, cytoplasmic mitotic chromosome, Late Promoter, Genetic Late Promoter, AGL4, cds1, branched-chain alpha-keto acid dehydrogenase phosphatase, LSD1, protein, T-Lymphocyte, Genome Stability, Viabilities, 3-hydroxy 3-methylglutaryl coenzymeA reductase phosphatase, CAIN, phosphospectrin phosphatase, Cell Growth in Number, Social Controls, Genetic Promoter, Protein Phosphatase 3, dmTAF[[II]]230, Histone H2b, Histone H2a, protein polypeptide chains, Readability, Genetic Middle, T Lymphocyte, calna1, Regions, Multicatalytic Endopeptidase Complex, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, Promoters, AA959943, Cell Number Growth, symptoms, Late Promoters, protein aggregate, Histone H3., Genetic Promoter Region, Formal Social Controls, Viability, rRNA Promoters, CDS1, Cds1, treatment, phosphatase 2A, SPK1, Growth, phosphatase 2B, TFIID TAF250, NFATc1, cel, Macropain, Chk2, T-Cells, caln, Promoter, Genetic Pseudopromoters, F10N7_150, phosphatase SP, Saccharomyes cerevisiae, T, proteins, protein phosphatase type 2B activity, serine/threonine specific protein phosphatase activity, Saccharomyces uvarum var. melibiosus, Proteasome Endopeptidase, 20S Proteasome, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity, Pseudopromoter, Acts, Genetic Promotors, Social, HuCds1, chk2, T Cells, Saccharomyces capensis, Calcineurin B, Calcineurin A, disease management, Histone H5, Therapies, AGAMOUS-like 4, Histone H4, Histone H7, 26S proteasome, CHK2, zinc ion regulated proximal promoter sequence-specific DNA binding, sequence-specific transcription regulatory region DNA binding RNA polymerase II transcription factor recruiting transcription factor activity, brewer's yeast, transcription from bacterial-type RNA polymerase promoter, Thymus Dependent Lymphocytes, Histone H1, intracellular, TRANSCRIPTION FACTOR, Histone H3, RNA polymerase II distal enhancer sequence-specific binding, Acta-2, Therapy, RNA polymerase II core promoter proximal region sequence-specific binding, screening, dTAF[[II]]230, Proteinase, Endopeptidase Complex, Promotor, TAF200, Actsk-1, Phosphatase 3, response to DNA damage stimulus, TAFII-250, TAF250/230, metal ion regulated sequence-specific DNA binding RNA polymerase II transcription factor activity, Protein Phosphatase 3 Inhibitors, Genetic Promoters, Ingensin, PP1425, NF-ATc1, Promotors, TAFII250, Protein Phosphatase-2B Inhibitors, Protein Phosphatase-2B, T-Cell, Calcineurin Blockers, Genetic Materials, Cellular, sequence-specific distal enhancer binding RNA polymerase II transcription factor activity, internal to cell, Genetic Middle Promoters, Region, Genetic Material, phosphatase III, ppp2b, proteasome, F14P3.4, Yeast, Early Promoter, pp1425, Calcineurin, Factors, NFAT transcription complex cytosolic component, Genetic Promotor, Early Promoters, Genetic Pseudopromoter, Thymus-Dependent, Promoter Region, Control, F14P3_4, Middle Promoter, signs, Controls, CG17603, TAF[[II]], hucds1, rRNA Promoter, Treatments, Transcription factor, Genomic, Thymus-Dependent Lymphocyte, calcium-dependent protein serine/threonine phosphatase, Taf250, Material, SR3-5, Proliferation, bacterial transcription, Cells, Middle Promoters, copper ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, Cell Number, Cistron, T Cell, protein phosphatase type 4, protein phosphatase type 1, protein phosphatase type 2A activity, Genomic Stabilities, polycation modulated (PCM-) phosphatase, Regulation, Inhibitor, metal ion regulated sequence-specific DNA binding, metaphase chromosome, TAF230, metal ion regulated proximal promoter sequence-specific DNA binding, Regulations, protein levels, d230, Thymus-Dependent Lymphocytes, Protein Phosphatase 3 Regulatory Subunit, rad53, casein phosphatase, phosphatase IB, baker's yeast, Gene, dTAFII250, phosphatase C-II, phosphatase II, SEPALLATA 2, protein D phosphatase, Genomic Stability, LFS2, protein-containing complex, EfW1, Transcription Factor, Saccharomyces italicus, hCds1, Stability, Multicatalytic Proteinase, protein phosphatase type 1 activity, zinc ion regulated core promoter proximal region sequence-specific DNA binding, polypeptide chain, dmTAF1, Taf230, lfs2, Instabilities, Survival, yeast, Genomic Instabilities, calcium levels, DNA Damage Response, Gene Products, phosphatase H-II, HMG-CoA reductase phosphatase, Number Growth, Genetic Early, Genome Instabilities, Histone H3.3, lager beer yeast, TAF250, protoplasm, study, Taf200, Transcription, HUCDS1, dTAF[[II]]250, Genetic, protoplast, cell, calcineurin, Complex, Nfatcb, Taf1p, dTAF250, 2210017P03Rik, protein phosphatase type 4 activity, phosphatase IV, cell proliferation, Candida robusta, Multicatalytic Endopeptidase, RNA polymerase II proximal promoter sequence-specific DNA binding, Multicatalytic, Aspergillus awamori acid protein phosphatase, copper ion regulated proximal promoter sequence-specific DNA binding, Macroxyproteinase, Calcineurin Inhibitor, Protein Phosphatase 3 Catalytic Subunit, TAF, T Lymphocytes, Pseudopromoters, Lymphocyte, Multiplication, TAF[[II]]250, Cellular Proliferation, findings, Formal Social Control, protein complex, protein phosphatase type 2C activity, Proteins, nf-atc, l(3)84Ab, Promotor Regions, zinc ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, homeobox 1, BG:DS00004.13, Factor, nfat2, AI449492, Cistrons, Histone, Cell, Saccaromyces cerevisiae, Proteasome, dTAF230, Stabilities, Cell Viabilities, transcription factor activity, calna, Sccharomyces cerevisiae, native protein, protein phosphatase type 2B, natural protein, protein phosphatase type 2A, Social Control, p230, Protein, TAF[[II]]250/230, RNA polymerase II transcription factor activity, TFIID, NFATc, Promotor Region, BCKDH phosphatase, cna1, intrinsic catalyst activity, Genetic Promoter Regions, metal ion regulated core promoter proximal region sequence-specific DNA binding RNA polymerase II transcription factor activity, Genome Stabilities, KNOTTED1-like homeobox gene 5, Saccharomyces oviformis, Taf[[II]]250, MEC2, Calcineurin inhibitor, TAF[[II]]230, Prosome, NFAT2, ccn1, Calcineurin Antagonists, NF-ATC, NFATC, 20S, Lymphocytes, TAF[II]250, Understanding, metal ion regulated core promoter proximal region sequence-specific binding, copper ion regulated core promoter proximal region sequence-specific binding, Histone H1(s), F10N7.150, Protein Gene Products, phosphopyruvate dehydrogenase phosphatase, Rad53, Gene Proteins, Protein Phosphatase 2B, nfatc, Promoter Regions, DmelCG17603, Genome Instability, rRNA, Therapeutic, Cell Multiplication, RAD53, Protein Phosphatase 2B Inhibitors, NF-ATc, Treatment, regulation, Instability, multicatalytic endopeptidase, Cell Viability, protein phosphatase X, Genome, AV076380, proteasome endopeptidase complex, phosphatase I, TAF1falseProteomic analysis of FK506 treated cancer cellsHs578T cells were treated with FK506 for 3h and 12h, and proteomics analysis performed to identify proteins affected by FK506 treatmentMon Dec 30 00:00:00 GMT 2024PXD042833960638926604