Sphingosine Kinase 2 Regulates Aryl Hydrocarbon Receptor Nuclear Translocation and Target Gene Activation.
AHR
SPHK2
ceramide
sphingolipid
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
29 Aug 2024
29 Aug 2024
Historique:
revised:
06
08
2024
received:
22
01
2024
medline:
31
8
2024
pubmed:
31
8
2024
entrez:
29
8
2024
Statut:
aheadofprint
Résumé
Sphingolipids play vital roles in metabolism and regulation. Previously, the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, was reported to directly regulate ceramide synthesis genes by binding to their promoters. Herein, sphingosine kinase 2 (SPHK2), responsible for producing sphingosine-1-phosphate (S1P), was found to interact with AHR through LXXLL motifs, influencing AHR nuclear localization. Through mutagenesis and co-transfection studies, AHR activation and subsequent nuclear translocation was hindered by SPHK2 LXXLL mutants or SPHK2 lacking a nuclear localization signal (NLS). Similarly, an NLS-deficient AHR mutant impaired SPHK2 nuclear translocation. Silencing SPHK2 reduced AHR expression and its target gene CYP1A1, while SPHK2 overexpression enhanced AHR activity. SPHK2 was found enriched on the CYP1A1 promoter, underscoring its role in AHR target gene activation. Additionally, S1P rapidly increased AHR expression at both the mRNA and protein levels and promoted AHR recruitment to the CYP1A1 promoter. Using mouse models, AHR deficiency compromised SPHK2 nuclear translocation, illustrating a critical interaction where SPHK2 facilitates AHR nuclear localization and supports a positive feedback loop between AHR and sphingolipid enzyme activity in the nucleus. These findings highlight a novel function of SPHK2 in regulating AHR activity and gene expression.
Identifiants
pubmed: 39207053
doi: 10.1002/advs.202400794
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2400794Subventions
Organisme : Fukuoka Public Health Promotion Organization Cancer Research Fund
ID : 21K15424
Organisme : Science Achievement Graduate Fellowship, Pennsylvania State University
Organisme : Intramural Research Program, National Cancer Institute, Cencer for Cancer Research, Cancer Innovation Laboratory
Organisme : National Institute of Food and Agriculture
ID : PEN4917#7006412
Organisme : NIH Office of the Director
ID : S10OD021750
Organisme : National Institute of Environmental Health Sciences
ID : ES028288
Organisme : National Institute of Environmental Health Sciences
ID : ES035027
Organisme : National Institute of Environmental Health Sciences
ID : ES028244
Informations de copyright
© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.
Références
W. Li, Q. Long, H. Wu, Y. Zhou, L. Duan, H. Yuan, Y. Ding, Y. Huang, Y. Wu, J. Huang, D. Liu, B. Chen, J. Zhang, J. Qi, S. Du, L. Li, Y. Liu, Z. Ruan, Z. Liu, Z. Liu, Y. Zhao, J. Lu, J. Wang, W. Y. Chan, X. Liu, Nat. Commun. 2022, 13, 7414.
A. Gomez‐Larrauri, U. Das Adhikari, M. Aramburu‐Nuñez, A. Custodia, A. Ouro, Medicina 2021, 57, 729.
S. A. Summers, B. Chaurasia, W. L. Holland, Nat. Metab. 2019, 1, 1051.
E. Albi, M. Mersel, C. Leray, M. L. Tomassoni, M. P. Viola‐Magni, Lipids 1994, 29, 715.
E. Albi, M. P. Magni, Biochem. Biophys. Res. Commun. 1997, 236, 29.
E. Albi, M. V. Magni, J. Hepatol. 2002, 36, 395.
J. Wei, T. Yerokun, M. Leipelt, C. A. Haynes, H. Radhakrishna, A. Momin, S. Kelly, H. Park, E. Wang, J. M. Carton, D. J. Uhlinger, A. H. Merrill, Biochim. Biophys. Acta. 2009, 1791, 746.
E. Albi, M. Villani, Commun. Integr. Biol. 2009, 2, 23.
P. Fu, D. L. Ebenezer, A. W. Ha, V. Suryadevara, A. Harijith, V. Natarajan, J. Cell. Biochem. 2018, 119, 6337.
I. A. Murray, A. D. Patterson, G. H. Perdew, Nat. Rev. Cancer. 2014, 14, 801.
H. S. Chen, G. H. Perdew, J. Biol. Chem. 1994, 269, 27554.
A. Kazlauskas, L. Poellinger, I. Pongratz, J. Biol. Chem. 1999, 274, 13519.
T. D. Hubbard, I. A. Murray, G. H. Perdew, Drug Metab. Dispos. 2015, 43, 1522.
A. Metidji, S. Omenetti, S. Crotta, Y. Li, E. Nye, E. Ross, V. Li, M. R. Maradana, C. Schiering, B. Stockinger, Immunity 2018, 49, 353.
J. Qiu, J. J. Heller, X. Guo, Z. E. Chen, K. Fish, Y. X. Fu, L. Zhou, Immunity 2012, 36, 92.
K. L. Vaughan, A. M. Franchini, H. G. Kern, B. P. Lawrence, Stem Cells Dev. 2021, 30, 970.
X. Zhou, D. Chakraborty, I. A. Murray, D. Coslo, Z. Kehs, A. Vijay, C. Ton, D. Desai, S. G. Amin, A. D. Patterson, G. H. Perdew, Lab. Investig. J. Tech. Methods Pathol. 2023, 103, 100012.
E. H. van den Bogaard, M. A. Podolsky, J. P. Smits, X. Cui, C. John, K. Gowda, D. Desai, S. G. Amin, J. Schalkwijk, G. H. Perdew, A. B. Glick, J. Invest. Dermatol. 2015, 135, 1320.
Q. Liu, L. Zhang, E. L. Allman, T. D. Hubbard, I. A. Murray, F. Hao, Y. Tian, W. Gui, R. G. Nichols, P. B. Smith, M. Anitha, G. H. Perdew, A. D. Patterson, Toxicology 2021, 458, 152831.
S. Majumder, M. Kono, Y. T. Lee, C. Byrnes, C. Li, G. Tuymetova, R. L. Proia, J. Biol. Chem. 2020, 295, 4341.
M. Sociale, A. L. Wulf, B. Breiden, K. Klee, M. Thielisch, F. Eckardt, J. Sellin, M. H. Bülow, S. Löbbert, N. Weinstock, A. Voelzmann, J. Schultze, K. Sandhoff, R. Bauer, Cell Rep. 2018, 22, 967.
R. S. Savkur, T. P. Burris, J. Pept. Res. 2004, 63, 207.
M. J. Plevin, M. M. Mills, M. Ikura, Trends Biochem. Sci. 2005, 30, 66.
C. H. Lee, L. N. Wei, J. Biol. Chem. 1999, 274, 31320.
M. B. Kumar, G. H. Perdew, Gene Expr. 1999, 8, 273.
A. Razeto, V. Ramakrishnan, C. M. Litterst, K. Giller, C. Griesinger, T. Carlomagno, N. Lakomek, T. Heimburg, M. Lodrini, E. Pfitzner, S. Becker, J. Mol. Biol. 2004, 336, 319.
C. Flaveny, R. K. Reen, A. Kusnadi, G. H. Perdew, Arch. Biochem. Biophys. 2008, 471, 215.
D. M. Heery, E. Kalkhoven, S. Hoare, M. G. Parker, Nature 1997, 387, 733.
G. Ding, H. Sonoda, H. Yu, T. Kajimoto, S. K. Goparaju, S. Jahangeer, T. Okada, S. I. Nakamura, J. Biol. Chem. 2007, 282, 27493.
N. Igarashi, T. Okada, S. Hayashi, T. Fujita, S. Jahangeer, S. Nakamura, J. Biol. Chem. 2003, 278, 46832.
I. Kudo, M. Hosaka, A. Haga, N. Tsuji, Y. Nagata, H. Okada, K. Fukuda, Y. Kakizaki, T. Okamoto, E. Grave, H. Itoh, J. Biochem. 2018, 163, 223.
M. Kono, L. E. Hoachlander‐Hobby, S. Majumder, R. Schwartz, C. Byrnes, H. Zhu, R. L. Proia, J. Lipid Res. 2022, 63, 100225.
K. J. French, Y. Zhuang, L. W. Maines, P. Gao, W. Wang, V. Beljanski, J. J. Upson, C. L. Green, S. N. Keller, C. D. Smith, J. Pharmacol. Exp. Ther. 2010, 333, 129.
N. C. Hait, J. Allegood, M. Maceyka, G. M. Strub, K. B. Harikumar, S. K. Singh, C. Luo, R. Marmorstein, T. Kordula, S. Milstien, S. Spiegel, Science 2009, 325, 1254.
T. Hla, Prostaglandins Other Lipid Mediat. 2005, 77, 197.
K. Adachi, K. Chiba, Perspect. Med. Chem. 2007, 1, 11.
A. H. Merril, M. Nikolova‐Karakashian, E. M. Schmelz, E. T. Morgan, J. Stewart, Chem. Phys. Lipids. 1999, 102, 131.
H. Ikushiro, H. Hayashi, H. Kagamiyama, Biochemistry 2004, 43, 1082.
S. Spiegel, S. Milstien, Nat. Rev. Mol. Cell Biol. 2003, 4, 397.
K. Mendelson, S. Pandey, Y. Hisano, F. Carellini, B. C. Das, T. Hla, T. Evans, Elife 2017, 6, e21992.
A. N. Urs, E. Dammer, M. B. Sewer, Endocrinology 2006, 147, 5249.
N. C. Hait, A. Maiti, P. Xu, Q. Qi, T. Kawaguchi, M. Okano, K. Takabe, L. Yan, C. Luo, FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2020, 34, 4293.
A. A. Farooqui, Neurosci. Rev. J. Bring. Neurobiol. Neurol. Psych. 2009, 15, 392.
S. White‐Gilbertson, T. Mullen, C. Senkal, P. Lu, B. Ogretmen, L. Obeid, C. Voelkel‐Johnson, Oncogene 2009, 28, 1132.
S. A. F. Morad, M. C. Cabot, Nat. Rev. Cancer. 2013, 13, 51.
J. D. Saba, J. Lipid Res. 2019, 60, 456.
P. Ramadoss, G. H. Perdew, Biochemistry 2005, 44, 11148.
L. Zhang, R. G. Nichols, J. Correll, I. A. Murray, N. Tanaka, P. B. Smith, T. D. Hubbard, A. Sebastian, I. Albert, E. Hatzakis, F. J. Gonzalez, G. H. Perdew, A. D. Patterson, Environ. Health Perspect. 2015, 123, 679.
G. H. Perdew, Arch. Biochem. Biophys. 1991, 291, 284.