Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 325 (5945): 1254-1257

Copyright © 2009 by the American Association for the Advancement of Science

Regulation of Histone Acetylation in the Nucleus by Sphingosine-1-Phosphate

Nitai C. Hait,1 Jeremy Allegood,1 Michael Maceyka,1 Graham M. Strub,1 Kuzhuvelil B. Harikumar,1 Sandeep K. Singh,1 Cheng Luo,2,3 Ronen Marmorstein,2 Tomasz Kordula,1 Sheldon Milstien,4 Sarah Spiegel1,*

Abstract: The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) can act intracellularly independently of its cell surface receptors through unknown mechanisms. Sphingosine kinase 2 (SphK2), one of the isoenzymes that generates S1P, was associated with histone H3 and produced S1P that regulated histone acetylation. S1P specifically bound to the histone deacetylases HDAC1 and HDAC2 and inhibited their enzymatic activity, preventing the removal of acetyl groups from lysine residues within histone tails. SphK2 associated with HDAC1 and HDAC2 in repressor complexes and was selectively enriched at the promoters of the genes encoding the cyclin-dependent kinase inhibitor p21 or the transcriptional regulator c-fos, where it enhanced local histone H3 acetylation and transcription. Thus, HDACs are direct intracellular targets of S1P and link nuclear S1P to epigenetic regulation of gene expression.

1 Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
2 The Wistar Institute and Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China.
4 National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.

* To whom correspondence should be addressed. E-mail: sspiegel{at}vcu.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Roles of Sphingosine-1-Phosphate in Reproduction.
L. Guo, X. Ou, H. Li, and Z. Han (2014)
Reproductive Sciences 21, 550-554
   Abstract »    Full Text »    PDF »
The acetylome regulators Hdac1 and Hdac2 differently modulate intestinal epithelial cell dependent homeostatic responses in experimental colitis.
N. Turgeon, J. M. Gagne, M. Blais, F.-P. Gendron, F. Boudreau, and C. Asselin (2014)
Am J Physiol Gastrointest Liver Physiol 306, G594-G605
   Abstract »    Full Text »    PDF »
Role of sphingolipids in oestrogen signalling in breast cancer cells: an update.
O. Sukocheva and C. Wadham (2014)
J. Endocrinol. 220, R25-R35
   Abstract »    Full Text »    PDF »
Hepatic Apolipoprotein M (ApoM) Overexpression Stimulates Formation of Larger ApoM/Sphingosine 1-Phosphate-enriched Plasma High Density Lipoprotein.
M. Liu, J. Seo, J. Allegood, X. Bi, X. Zhu, E. Boudyguina, A. K. Gebre, D. Avni, D. Shah, M. G. Sorci-Thomas, et al. (2014)
J. Biol. Chem. 289, 2801-2814
   Abstract »    Full Text »    PDF »
Molecular mechanism of sphingosine-1-phosphate action in Duchenne muscular dystrophy.
D.-H. Nguyen-Tran, N. C. Hait, H. Sperber, J. Qi, K. Fischer, N. Ieronimakis, M. Pantoja, A. Hays, J. Allegood, M. Reyes, et al. (2014)
Dis. Model. Mech. 7, 41-54
   Abstract »    Full Text »    PDF »
Sphingosine 1-phosphate signalling.
K. Mendelson, T. Evans, and T. Hla (2014)
Development 141, 5-9
   Abstract »    Full Text »    PDF »
Sphingosine phosphate lyase regulates myogenic differentiation via S1P receptor-mediated effects on myogenic microRNA expression.
A. S. de la Garza-Rodea, D. M. Baldwin, B. Oskouian, R. F. Place, P. Bandhuvula, A. Kumar, and J. D. Saba (2014)
FASEB J 28, 506-519
   Abstract »    Full Text »    PDF »
Targeting Sphingosine Kinase Induces Apoptosis and Tumor Regression for KSHV-Associated Primary Effusion Lymphoma.
Z. Qin, L. Dai, J. Trillo-Tinoco, C. Senkal, W. Wang, T. Reske, K. Bonstaff, L. Del Valle, P. Rodriguez, E. Flemington, et al. (2014)
Mol. Cancer Ther. 13, 154-164
   Abstract »    Full Text »    PDF »
ETS-1-mediated Transcriptional Up-regulation of CD44 Is Required for Sphingosine-1-phosphate Receptor Subtype 3-stimulated Chemotaxis.
W. Zhang, J. Zhao, J.-F. Lee, A. Gartung, H. Jawadi, W. L. Lambiv, K. V. Honn, and M.-J. Lee (2013)
J. Biol. Chem. 288, 32126-32137
   Abstract »    Full Text »    PDF »
Sphingosine Kinases Are Not Required for Inflammatory Responses in Macrophages.
Y. Xiong, H. J. Lee, B. Mariko, Y.-C. Lu, A. J. Dannenberg, A. S. Haka, F. R. Maxfield, E. Camerer, R. L. Proia, and T. Hla (2013)
J. Biol. Chem. 288, 32563-32573
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate can promote mast cell hyper-reactivity through regulation of contactin-4 expression.
A. Olivera, Y. Kitamura, L. D. Wright, M. L. Allende, W. Chen, T. Kaneko-Goto, Y. Yoshihara, R. L. Proia, and J. Rivera (2013)
J. Leukoc. Biol. 94, 1013-1024
   Abstract »    Full Text »    PDF »
Sphingosine Kinase 1 Regulates Tumor Necrosis Factor-mediated RANTES Induction through p38 Mitogen-activated Protein Kinase but Independently of Nuclear Factor {kappa}B Activation.
M. M. Adada, K. A. Orr-Gandy, A. J. Snider, D. Canals, Y. A. Hannun, L. M. Obeid, and C. J. Clarke (2013)
J. Biol. Chem. 288, 27667-27679
   Abstract »    Full Text »    PDF »
Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P).
L. Zhang, N. Urtz, F. Gaertner, K. R. Legate, T. Petzold, M. Lorenz, A. Mazharian, S. P. Watson, and S. Massberg (2013)
Blood 122, 791-802
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate Phosphatase 1 Regulates Keratinocyte Differentiation and Epidermal Homeostasis.
M. L. Allende, L. M. Sipe, G. Tuymetova, K. L. Wilson-Henjum, W. Chen, and R. L. Proia (2013)
J. Biol. Chem. 288, 18381-18391
   Abstract »    Full Text »    PDF »
Sphingolipid Homeostasis in the Endoplasmic Reticulum and Beyond.
D. K. Breslow (2013)
Cold Spring Harb Perspect Biol 5, a013326
   Abstract »    Full Text »    PDF »
Spns2, a transporter of phosphorylated sphingoid bases, regulates their blood and lymph levels, and the lymphatic network.
M. Nagahashi, E. Y. Kim, A. Yamada, S. Ramachandran, J. C. Allegood, N. C. Hait, M. Maceyka, S. Milstien, K. Takabe, and S. Spiegel (2013)
FASEB J 27, 1001-1011
   Abstract »    Full Text »    PDF »
A Novel Role of a Lipid Species, Sphingosine-1-Phosphate, in Epithelial Innate Immunity.
K. Park, P. M. Elias, K.-O. Shin, Y.-M. Lee, M. Hupe, A. W. Borkowski, R. L. Gallo, J. Saba, W. M. Holleran, and Y. Uchida (2013)
Mol. Cell. Biol. 33, 752-762
   Abstract »    Full Text »    PDF »
Sphingolipids: regulators of crosstalk between apoptosis and autophagy.
M. M. Young, M. Kester, and H.-G. Wang (2013)
J. Lipid Res. 54, 5-19
   Abstract »    Full Text »    PDF »
A new, long-wavelength borondipyrromethene sphingosine for studying sphingolipid dynamics in live cells.
R. Kim, K. Lou, and M. L. Kraft (2013)
J. Lipid Res. 54, 265-275
   Abstract »    Full Text »    PDF »
Genetic elevation of Sphingosine 1-phosphate suppresses dystrophic muscle phenotypes in Drosophila.
M. Pantoja, K. A. Fischer, N. Ieronimakis, M. Reyes, and H. Ruohola-Baker (2013)
Development 140, 136-146
   Abstract »    Full Text »    PDF »
Regulation of Autophagy and Its Associated Cell Death by "Sphingolipid Rheostat": RECIPROCAL ROLE OF CERAMIDE AND SPHINGOSINE 1-PHOSPHATE IN THE MAMMALIAN TARGET OF RAPAMYCIN PATHWAY.
M. Taniguchi, K. Kitatani, T. Kondo, M. Hashimoto-Nishimura, S. Asano, A. Hayashi, S. Mitsutake, Y. Igarashi, H. Umehara, H. Takeya, et al. (2012)
J. Biol. Chem. 287, 39898-39910
   Abstract »    Full Text »    PDF »
Acid Ceramidase (ASAH1) Represses Steroidogenic Factor 1-Dependent Gene Transcription in H295R Human Adrenocortical Cells by Binding to the Receptor.
N. C. Lucki, D. Li, S. Bandyopadhyay, E. Wang, A. H. Merrill, and M. B. Sewer (2012)
Mol. Cell. Biol. 32, 4419-4431
   Abstract »    Full Text »    PDF »
The functional roles of S1P in immunity.
Y. Hisano, T. Nishi, and A. Kawahara (2012)
J. Biochem. 152, 305-311
   Abstract »    Full Text »    PDF »
Stimulation of Histone Deacetylase Activity by Metabolites of Intermediary Metabolism.
M. Vogelauer, A. S. Krall, M. A. McBrian, J.-Y. Li, and S. K. Kurdistani (2012)
J. Biol. Chem. 287, 32006-32016
   Abstract »    Full Text »    PDF »
Oncogenic K-Ras Regulates Bioactive Sphingolipids in a Sphingosine Kinase 1-dependent Manner.
C. R. Gault, S. T. Eblen, C. A. Neumann, Y. A. Hannun, and L. M. Obeid (2012)
J. Biol. Chem. 287, 31794-31803
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate lyase expression in embryonic and adult murine tissues.
A. D. Borowsky, P. Bandhuvula, A. Kumar, Y. Yoshinaga, M. Nefedov, L. G. Fong, M. Zhang, B. Baridon, L. Dillard, P. de Jong, et al. (2012)
J. Lipid Res. 53, 1920-1931
   Abstract »    Full Text »    PDF »
Direct Modification and Activation of a Nuclear Receptor-PIP2 Complex by the Inositol Lipid Kinase IPMK.
R. D. Blind, M. Suzawa, and H. A. Ingraham (2012)
Science Signaling 5, ra44
   Abstract »    Full Text »    PDF »
Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release.
J. P. Chan, Z. Hu, and D. Sieburth (2012)
Genes & Dev. 26, 1070-1085
   Abstract »    Full Text »    PDF »
Phosphoinositides as Regulators of Protein-Chromatin Interactions.
K. Viiri, M. Maki, and O. Lohi (2012)
Science Signaling 5, pe19
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate (S1P) Regulates Glucose-stimulated Insulin Secretion in Pancreatic Beta Cells.
J. Cantrell Stanford, A. J. Morris, M. Sunkara, G. J. Popa, K. L. Larson, and S. Ozcan (2012)
J. Biol. Chem. 287, 13457-13464
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate Produced by Sphingosine Kinase 1 Promotes Breast Cancer Progression by Stimulating Angiogenesis and Lymphangiogenesis.
M. Nagahashi, S. Ramachandran, E. Y. Kim, J. C. Allegood, O. M. Rashid, A. Yamada, R. Zhao, S. Milstien, H. Zhou, S. Spiegel, et al. (2012)
Cancer Res. 72, 726-735
   Abstract »    Full Text »    PDF »
Concerted functions of HDAC1 and microRNA-574-5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells.
M. Meyers-Needham, S. Ponnusamy, S. Gencer, W. Jiang, R. J. Thomas, C. E. Senkal, and B. Ogretmen (2012)
EMBO Mol Med. 4, 78-92
   Abstract »    Full Text »    PDF »
Autophagy Induced by Deficiency of Sphingosine-1-phosphate Phosphohydrolase 1 Is Switched to Apoptosis by Calpain-mediated Autophagy-related Gene 5 (Atg5) Cleavage.
S. Lepine, J. C. Allegood, Y. Edmonds, S. Milstien, and S. Spiegel (2011)
J. Biol. Chem. 286, 44380-44390
   Abstract »    Full Text »    PDF »
Sphingosine Kinase Inhibitors and Cancer: Seeking the Golden Sword of Hercules.
S. Pyne, R. Bittman, and N. J. Pyne (2011)
Cancer Res. 71, 6576-6582
   Abstract »    Full Text »    PDF »
Ablation of Sphingosine Kinase-2 Inhibits Tumor Cell Proliferation and Migration.
P. Gao and C. D. Smith (2011)
Mol. Cancer Res. 9, 1509-1519
   Abstract »    Full Text »    PDF »
Lipid phosphate phosphatase 3 enables efficient thymic egress.
B. Breart, W. D. Ramos-Perez, A. Mendoza, A. K. Salous, M. Gobert, Y. Huang, R. H. Adams, J. J. Lafaille, D. Escalante-Alcalde, A. J. Morris, et al. (2011)
J. Exp. Med. 208, 1267-1278
   Abstract »    Full Text »    PDF »
Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A.
A. Salas, S. Ponnusamy, C. E. Senkal, M. Meyers-Needham, S. P. Selvam, S. A. Saddoughi, E. Apohan, R. D. Sentelle, C. Smith, C. R. Gault, et al. (2011)
Blood 117, 5941-5952
   Abstract »    Full Text »    PDF »
Photolysis of caged sphingosine-1-phosphate induces barrier enhancement and intracellular activation of lung endothelial cell signaling pathways.
P. V. Usatyuk, D. He, V. Bindokas, I. A. Gorshkova, E. V. Berdyshev, J. G. N. Garcia, and V. Natarajan (2011)
Am J Physiol Lung Cell Mol Physiol 300, L840-L850
   Abstract »    Full Text »    PDF »
FTY720 Analogues as Sphingosine Kinase 1 Inhibitors: ENZYME INHIBITION KINETICS, ALLOSTERISM, PROTEASOMAL DEGRADATION, AND ACTIN REARRANGEMENT IN MCF-7 BREAST CANCER CELLS.
K. G. Lim, F. Tonelli, Z. Li, X. Lu, R. Bittman, S. Pyne, and N. J. Pyne (2011)
J. Biol. Chem. 286, 18633-18640
   Abstract »    Full Text »    PDF »
BACE1 Activity Is Modulated by Cell-Associated Sphingosine-1-Phosphate.
N. Takasugi, T. Sasaki, K. Suzuki, S. Osawa, H. Isshiki, Y. Hori, N. Shimada, T. Higo, S. Yokoshima, T. Fukuyama, et al. (2011)
J. Neurosci. 31, 6850-6857
   Abstract »    Full Text »    PDF »
S1P lyase: a novel therapeutic target for ischemia-reperfusion injury of the heart.
P. Bandhuvula, N. Honbo, G.-Y. Wang, Z.-Q. Jin, H. Fyrst, M. Zhang, A. D. Borowsky, L. Dillard, J. S. Karliner, and J. D. Saba (2011)
Am J Physiol Heart Circ Physiol 300, H1753-H1761
   Abstract »    Full Text »    PDF »
Distribution and Functions of Sterols and Sphingolipids.
J. T. Hannich, K. Umebayashi, and H. Riezman (2011)
Cold Spring Harb Perspect Biol 3, a004762
   Abstract »    Full Text »    PDF »
Regulation of CC Ligand 5/RANTES by Acid Sphingomyelinase and Acid Ceramidase.
R. W. Jenkins, C. J. Clarke, D. Canals, A. J. Snider, C. R. Gault, L. Heffernan-Stroud, B. X. Wu, F. Simbari, P. Roddy, K. Kitatani, et al. (2011)
J. Biol. Chem. 286, 13292-13303
   Abstract »    Full Text »    PDF »
A Phase I Clinical Trial of Safingol in Combination with Cisplatin in Advanced Solid Tumors.
M. A. Dickson, R. D. Carvajal, A. H. Merrill Jr, M. Gonen, L. M. Cane, and G. K. Schwartz (2011)
Clin. Cancer Res. 17, 2484-2492
   Abstract »    Full Text »    PDF »
Suppression of Glucosylceramide Synthase Restores p53-Dependent Apoptosis in Mutant p53 Cancer Cells.
Y.-Y. Liu, G. A. Patwardhan, K. Bhinge, V. Gupta, X. Gu, and S. M. Jazwinski (2011)
Cancer Res. 71, 2276-2285
   Abstract »    Full Text »    PDF »
A Serotype 5/3 Adenovirus Expressing MDA-7/IL-24 Infects Renal Carcinoma Cells and Promotes Toxicity of Agents That Increase Ros and Ceramide Levels.
M. A. Park, H. A. Hamed, C. Mitchell, N. Cruickshanks, R. Dash, J. Allegood, I. P. Dmitriev, G. Tye, B. Ogretmen, S. Spiegel, et al. (2011)
Mol. Pharmacol. 79, 368-380
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration.
G. M. Strub, M. Paillard, J. Liang, L. Gomez, J. C. Allegood, N. C. Hait, M. Maceyka, M. M. Price, Q. Chen, D. C. Simpson, et al. (2011)
FASEB J 25, 600-612
   Abstract »    Full Text »    PDF »
HDL3, but not HDL2, stimulates plasminogen activator inhibitor-1 release from adipocytes: the role of sphingosine-1-phosphate.
M.-H. Lee, S. M. Hammad, A. J. Semler, L. M. Luttrell, M. F. Lopes-Virella, and R. L. Klein (2010)
J. Lipid Res. 51, 2619-2628
   Abstract »    Full Text »    PDF »
Estradiol Induces Export of Sphingosine 1-Phosphate from Breast Cancer Cells via ABCC1 and ABCG2.
K. Takabe, R. H. Kim, J. C. Allegood, P. Mitra, S. Ramachandran, M. Nagahashi, K. B. Harikumar, N. C. Hait, S. Milstien, and S. Spiegel (2010)
J. Biol. Chem. 285, 10477-10486
   Abstract »    Full Text »    PDF »
New Endogenous Regulators of Class I Histone Deacetylases.
A. Riccio (2010)
Science Signaling 3, pe1
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882