ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta V. 13, No 2, 2020
Р. 65-79, Bibliography 74, English
Universal Decimal Classification: 577.25: 577.23
https://doi.org/10.15407/biotech13.02.065
V. S. Nedzvetsky1, 2, C. A. Agca1, G. Baydas3
1Bing?l University, Selahaddin-i Eyyubi Mah, Merkez/Bing?l, Turkey
2Oles Honchar Dnipro National University, Dnipro, Ukraine
3Altinbash University, Mahmutbey, Ba?c?lar/?stanbul, Turkey
Peptidoglycan is a universal component of bacterial walls that exerts various biological activities, including tumoricidal effect. Anti-cancer effect of various peptidoglycan fractions and their derivates is different. Muramyl pentapeptide (MPP) is the most complete building block of peptidoglycan. MPP can stimulate cell reactivity as well as other muropeptides. In the present study, we evaluated inhibitory MPP effect on viability and migration of glioblastoma cells U373MG. As markers of cell reactivity we determined the amounts of proteins PARP1 and NF-kB. MPP exposure induced decrease in viability and migration activity of glioblastoma cells. Besides, MPP treatment increased the amounts of PARP1 and NF-kB in a dose-dependent manner. Furthermore, NADH level in exposed glioblastoma cells was depleted as compared to control. Thus, MPP exhibits tumoricidal effect in glioblastoma cells U373MG via depletion NADH content and consequently metabolic energy level. Moreover, upregulation of the amounts of PARP1 and NF-kB in glioblastoma cells could be an important mechanism of the inhibition of cell migrative capability and the progress of the tumor.
The obtained results evidenced that muramyl pentapeptide could initiate lack of migration via metabolic energy expenditure as a result of gliotypic reactivity. Further studies are actual and extremely required to clarify tumoricidal effect of this muropeptide in glia-derived tumors.
Key words: peptidoglycan, muramyl pentapeptide, PARP1, NF-kB, glioblastoma U373MG, cell reactivity.
© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2020
{accordion title="References" open="false"}
1. Fichera G. A., Fichera M., Milone G. Antitumoural activity of a cytotoxic peptide of Lactobacillus casei peptidoglycan and its interaction with mitochondrial-bound hexokinase. Anticancer Drugs. 2016, 27 (7), 609–619. https://doi.org/10.1097/CAD.0000000000000367
2. Commane D., Hughes R., Shortt C., Rowland I. The potential mechanisms involved in the anti-carcinogenic action of probiotics. Mutation Research ? Fundamental and Molecular Mechanisms of Mutagenesis. 2005, V. 91, P. 276–289. https://doi.org/10.1016/j.mrfmmm.2005.02.027
3. Salminen S., Morelli L., Marteau P., Brassart D., de Vos W. M., Fond?n R., Saxelin M., Collins K., Mogensen G., Birkeland S. E., Mattila-Sandholm T. Demonstration of safety of probiotics ? A review. Int. J. Food Microbiol. 1998, 44 (1–2), 93–106.
4. Kim J. Y., Woo H. J., Kim Y. S., Lee H. J. Screening for antiproliferative effects of cellular components from lactic acid bacteria against human cancer cell lines. Biotechnol. Lett. 2002, 24 (17), 1431–1436. https://doi.org/10.1023/A:1019875204323
5. Orlando A., Messa C., Linsalata M., Cavallini A., Russo F. Effects of Lactobacillus rhamnosus GG on proliferation and polyamine metabolism in HGC-27 human gastric and DLD-1 colonic cancer cell lines. Immunopharmacol. Immunotoxicol. 2009, 31 (1), 108–116. https://doi.org/10.1080/08923970802443631
6. Amrouche T., Boutin Y., Prioult G., Fliss I. Effects of bifidobacterial cytoplasm, cell wall and exopolysaccharide on mouse lymphocyte proliferation and cytokine production. Int. Dairy J. 2006, 16 (1), 70–80. https://doi.org/10.1016/j.idairyj.2005.01.008
7. Gonet-Sur?wka A. K., Strus M., Heczko P. B. P1250 Infiuence of Lactobacilli probiotic strains on apoptosis of colon cancer cells lines. Int. J. Antimicrob. Agents. 2007, P. 343–344. https://doi.org/10.1016/S0924-8579(07)71090-7https://doi.org/10.1016/S0924-8579(07)71090-7
8. Thirabunyanon M., Boonprasom P., Niamsup P. Probiotic potential of lactic acid bacteria isolated from fermented dairy milks on antiproliferation of colon cancer cells. Biotechnol. Lett. 2009, 31 (4), 571–576. https://doi.org/10.1007/s10529-008-9902-3
9. Tuo Y. F., Zhang L. W., Yi H. X., Zhang Y. C., Zhang W. Q., Han X., Du M., Jiao Y. H., Wang S. M. Short communication: Antiproliferative effect of wild Lactobacillus strains isolated from fermented foods on HT-29 cells. J. Dairy Sci. 2010, 93 (6), 2362–2366. https://doi.org/10.3168/jds.2010-3069
10. Ando K., Mori K., Corradini N., Redini F., Heymann D. Mifamurtide for the treatment of nonmetastatic osteosarcoma. Expert Opin. Pharmacother. 2011, 12 (2), 285–292. https://doi.org/10.1517/14656566.2011.543129
11. Wang S., Han X., Zhang L., Zhang Y., Li H., Jiao Y. Whole Peptidoglycan Extracts from the Lactobacillus paracasei subsp. paracasei M5 Strain Exert Anticancer Activity In Vitro. Biomed. Res. Int. 2018. https://doi.org/10.1155/2018/2871710
12. Fujimura T., Yamasaki K., Hidaka T., Ito Y., Aiba S. A synthetic NOD2 agonist, muramyl dipeptide (MDP)-Lys (L18) and IFN-? synergistically induce dendritic cell maturation with augmented IL-12 production and suppress melanoma growth. J. Dermatol. Sci. 2011, 62 (2), 107–115. https://doi.org/10.1016/j.jdermsci.2011.02.002
13. Yanagawa H., Haku T., Takeuchi E., Suzuki Y., Nokihara H., Sone S. Intrapleural therapy with MDP-Lys (L18), a synthetic derivative of muramyl dipeptide, against malignant pleurisy associated with lung cancer. Lung Cancer. 2000, 27 (2), 67–73. https://doi.org/10.1016/S0169-5002(99)00090-2
14. Kohashi O., Kohashi Y., Shigematsu N., Ozawa A., Kotani S. Acute and chronic polyarthritis induced by an aqueous form of 6-O-acyl and N-acyl derivatives of N-acetylmuramyl-L-alanyl-D-isoglutamine in euthymic rats and athymic nude rats. Lab. Invest. 1986, 55 (3), 337–346. http://www.ncbi.nlm.nih.gov/pubmed/3489128
15. Kong Y. C., Audibert F., Giraldo A. A., Rose N. R., Chedid L. Effects of natural or synthetic microbial adjuvants on induction of autoimmune thyroiditis. Infect. Immun. 1985, 49 (1), 40–45. https://doi.org/10.1128/IAI.49.1.40-45.1985
16. McAdam K. P., Foss N. T., Garcia C., DeLellis R., Chedid L., Rees R. J., Wolff S. M. Amyloidosis and the serum amyloid A protein response to muramyl dipeptide analogs and different mycobacterial species. Infect. Immun. 1983, 39 (3), 1147–1154. https://doi.org/10.1128/IAI.39.3.1147-1154.1983
17. Zhou C. J., Chen J., Hou J. B., Zheng Y., Yu Y. N., He H., Zhang Y. P., Feng X. L., Zheng Q. S.The Immunological Functions of Muramyl Dipeptide Compound Adjuvant on Humoral, Cellular-mediated and Mucosal Immune Responses to PEDV Inactivated Vaccine in Mice. Protein Pept. Lett. 2018, 25 (10), 908–913. https://doi.org/10.2174/0929866525666180917160926
18. Fichera G. A., Giese G. Non-immunologically-mediated cytotoxicity of Lactobacillus casei and its derivative peptidoglycan against tumor cell lines. Cancer Lett. 1994, 85 (1), 93–103. https://doi.org/10.1016/0304-3835(94)90244-5
19. Masjuk D. M., Nedzvetsky V. S. KAV. A method of enhancing the natural resistance of newborn piglets. Ukraine Patent 118400. August 10, 2017.
20. Nava Catorce M., Gevorkian G. LPS-induced Murine Neuroinflammation Model: Main Features and Suitability for Pre-clinical Assessment of Nutraceuticals. Curr. Neuropharmacol. 2016, 14 (2),155–164. https://doi.org/10.2174/1570159X14666151204122017
21. Agca C. A., Tykhomyrov A. A., Baydas G., Nedzvetsky V. S. Effects of a Propolis Extract on the Viability of and Levels of Cytoskeletal and Regulatory Proteins in Rat Brain Astrocytes: an In Vitro Study. Neurophysiol. 2017, 49 (4), 261–271. https://doi.org/10.1007/s11062-017-9680-4
22. Nedzvetsky V. S., Agca C. A., Kyrychenko S. V. Neuroprotective Effect of Curcumin on LPS-activated Astrocytes Is Related to the Prevention of GFAP and NF-?B Upregulation. Neurophysiol. 2017, 49 (4), 305–307. https://doi.org/10.1007/s11062-017-9687-x
23. Morgan M. J., Liu Z. G. Crosstalk of reactive oxygen species and NF-?B signaling. Cell Res. 2011, V. 21, P. 103–115. https://doi.org/10.1038/cr.2010.178
24. Owens R., Grabert K., Davies C. L., Alfieri A., Antel J. P., Healy L. M., McColl B. W. Divergent neuroinflammatory regulation of microglial TREM expression and involvement of NF-?B. Front Cell Neurosci. 2017, V. 2, P. 11. https://doi.org/10.3389/fncel.2017.00056
25. Gibson B. A., Kraus W. L. New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat. Rev. Mol. Cell Biol. 2012, V. 13, P. 411–424. https://doi.org/10.1038/nrm3376
26. Bock F. J., Todorova T. T., Chang P. RNA Regulation by Poly(ADP-Ribose) Polymerases. Mol. Cell. 2015, P. 959–969. https://doi.org/10.1016/j.molcel.2015.01.037
27. Bock F. J., Chang P. New directions in poly(ADP-ribose) polymerase biology. FEBS J. 2016, 283 (22), 4017–4031. https://doi.org/10.1111/febs.13737
28. Kauppinen T. M., Gan L., Swanson R. A. Poly(ADP-ribose) polymerase-1-induced NAD+ depletion promotes nuclear factor-?B transcriptional activity by preventing p65 de-acetylation. Biochim. Biophys. Acta. 2013, 1833 (8), 1985–1991. https://doi.org/10.1016/j.bbamcr.2013.04.005
29. Szab? C., Cuzzocrea S., Zingarelli B., O’Connor M., Salzman A. L. Endothelial dysfunction in a rat model of endotoxic shock: Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. J. Clin. Invest. 1997, 100 (3), 723–735. https://doi.org/10.1172/JCI119585
30. Chiarugi A., Moskowitz M. A. Poly(ADP-ribose) polymerase-1 activity promotes NF-?B-driven transcription and microglial activation: Implication for neurodegenerative disorders. J. Neurochem. 2003, 85 (2), 306–317. https://doi.org/10.1046/j.1471-4159.2003.01684.x
31. El-Jamal N., Bahr G. M., Echtay K. S. Effect of muramyl peptides on mitochondrial respiration. Clin. Exp. Immunol. 2009, 155 (1), 72–78. https://doi.org/10.1111/j.1365-2249.2008.03794.x
32. Tang K. S., Suh S. W., Alano C. C., Shao Z., Hunt W. T., Swanson R. A., Anderson C. M. Astrocytic poly(ADP-ribose) polymerase-1 activation leads to bioenergetic depletion and inhibition of glutamate uptake capacity. Glia. 2010, 58 (4), 446–457. https://doi.org/10.1002/glia.20936
33. Vavricka S. R., Musch M. W., Chang J. E., Nakagawa Y., Phanvijhitsiri K., Waypa T. S., Merl?n D., Schneew?nd O., Chang E. B. hPepT1 transports muramyl dipeptide, activating NF-?B and stimulating IL-8 secretion in human colonic Caco2/bbe cells. Gastroenterol. 2004, 127 (5), 1401–1409. https://doi.org/10.1053/j.gastro.2004.07.024
34. Ribes S., Adam N., Sch?tze S., Regen T., Redlich S., Janova H., Borisch A., Hanisch U. K., Nau R. The nucleotide-binding oligomerization domain-containing-2 ligand muramyl dipeptide enhances phagocytosis and intracellular killing of Escherichia coli K1 by Toll-like receptor agonists in microglial cells. J. Neuroimmunol. 2012, 14, 252 (1–2),16–23. https://doi.org/10.1016/j.jneuroim.2012.07.012
35. Ma G.-G., Shi B., Zhang X.-P., Qiu Y., Tu G.-W., Luo Z. The pathways and mechanisms of muramyl dipeptide transcellular transport mediated by PepT1 in enterogenous infection. Ann. Transl. Med. 2019, 7 (18), 50. https://doi.org/10.21037/atm.2019.07.103
36. Trajkovi? V., Samard?i? T., Sto?i?-Gruji?i? S., Rami? Z., Stojkovi? M. M. Muramyl dipeptide potentiates cytokine-induced activation of inducible nitric oxide synthase in rat astrocytes. Brain Res. 2000, 10, 883 (1), 157–163. https://doi.org/10.1016/S0006-8993(00)02920-6
37. Chauhan V. S., Sterka D. G., Furr S. R., Marriott I. NOD2 plays an important role in the inflammatory responses of microglia and astrocytes to bacterial CNS pathogens. Glia. 2009, 57 (4), 414–423. https://doi.org/10.1002/glia.20770
38. Masuzzo A., Mani?re G., Viallat-Lieutaud A., Avazeri ?., Zugasti O., Grosjean Y., L?opold C., Royet J. Peptidoglycan-dependent NF-kB activation in a small subset of brain octopaminergic neurons controls female oviposition. Elife. 2019, V. 1, P. 8. https://doi.org/10.7554/eLife.50559
39. Furnari F. B., Fenton T., Bachoo R. M., Mukasa A., Stommel J. M., Stegh A., Hahn W. C., Ligon K. L., Louis D. N., Brennan C., Chin L., DePinho R. A., Cavenee W. K. Malignant astrocytic glioma: Genetics, biology, and paths to treatment. Genes and Development. 2007, V. 21, P. 2683–2710. https://doi.org/10.1101/gad.1596707
40. Pointer K. B., Clark P. A., Zorniak M., Alrfaei B. M., Kuo J. S. Glioblastoma cancer stem cells: Biomarker and therapeutic advances. Neurochem. Inter. 2014, V. 71, P. 1–7. https://doi.org/10.1016/j.neuint.2014.03.005
41. Agnihotri S., Burrell K. E., Wolf A., Jalali S., Hawkins C., Rutka J. T., Zadeh G. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies. Archivum Immunologiae et Therapiae Experimentalis. 2013, V. 61, P. 25–41. https://doi.org/10.1007/s00005-012-0203-0
42. Wolf A. J., Reyes C. N., Liang W., Becker C., Shimada K., Wheeler M. L., Cho H. C., Popescu N. I., Coggeshall K. M., Arditi M., Underhill D. M. Hexokinase Is an Innate Immune Receptor for the Detection of Bacterial Peptidoglycan. Cell. 2016, V. 28, P. 624–36. https://doi.org/10.1016/j.cell.2016.05.076
43. Heim V. J., Stafford C. A., Nachbur U. NOD Signaling and Cell Death. Frontiers in Cell and Developmental Biology. 2019, V. 7, P. 423?444. https://doi.org/10.3389/fcell.2019.00208
44. Irazoki O., Hernandez S. B., Cava F. Peptidoglycan muropeptides: Release, perception, and functions as signaling molecules. Frontiers in Microbiology. 2019, 500 p. https://doi.org/10.3389/fmicb.2019.00500
45. Wolf A., Agnihotri S., Munoz D., Guha A. Developmental profile and regulation of the glycolytic enzyme hexokinase 2 in normal brain and glioblastoma multiforme. Neurobiol. Dis. 2011, 44 (1), 84–91. https://doi.org/10.1016/j.nbd.2011.06.007
46. Wolf A., Agnihotri S., Micallef J., Mukherjee J., Sabha N., Cairns R., Hawkins C., Guha A. Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J. Exp. Med. 2011, 14, 208 (2), 313–326. https://doi.org/10.1084/jem.20101470
47. Fehr A. R., Singh S. A., Kerr C. M., Mukai S., Higashi H., Aikawa M. The impact of PARPs and ADP-ribosylation on inflammation and host-pathogen interactions. Genes and Development. 2020, V. 34, P. 341–359. https://doi.org/10.1101/gad.334425.119
48. Billot-Klein D., Legrand R., Schoot B., Van Heijenoort J., Gutmann L. Peptidoglycan structure of Lactobacillus casei, a species highly resistant to glycopeptide antibiotics. J. Bacteriol. 1997, V. 179, P. 6208–6212. https://doi.org/10.1128/JB.179.19.6208-6212.1997
49. Bahr G. M., Chedid L. Immunological activities of muramyl peptides. Fed Proc. 1986, 45 (11), 2541–2544.
50. Heinzelmann M., Polk H. C., Chernobelsky A., Stites T. P., Gordon L. E. Endotoxin and muramyl dipeptide modulate surface receptor expression on human mononuclear cells. Immunopharmacol. 2000, 20, 48 (2), 117–128. https://doi.org/10.1016/S0162-3109(00)00195-8
51. Traub S., von Aulock S., Hartung T., Hermann C. Invited review: MDP and other muropeptides — direct and synergistic effects on the immune system. J. Endotoxin. Res. 2006, 12 (2), 69–85. https://doi.org/10.1177/09680519060120020301
52. Typas A., Banzhaf M., Gross C. A., Vollmer W. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat. Rev. Microbiol. 2012, V. 10, P. 123–136. https://doi.org/10.1038/nrmicro2677
53. Egan A. J. F., Cleverley R. M., Peters K., Lewis R. J., Vollmer W. Regulation of bacterial cell wall growth. FEBS J. 2017, V. 284, P. 851–867. https://doi.org/10.1111/febs.13959
54. Goldman W. E., Klapper D. G., Baseman J. B. Detection, isolation, and analysis of a released Bordetella pertussis product toxic to cultured tracheal cells. Infect. Immun. 1982, 36 (2), 782–794. https://doi.org/10.1128/IAI.36.2.782-794.1982
55. Bensaad K., Tsuruta A., Selak M. A., Vidal M. N. C., Nakano K., Bartrons R., Gottlieb E., Vousden K. H.TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis. Cell. 2006, 14, 126 (1),107–120. https://doi.org/10.1016/j.cell.2006.05.036
56. Bensaad K., Cheung E. C., Vousden K. H. Modulation of intracellular ROS levels by TIGAR controls autophagy. EMBO J. 2009, 28 (19), 3015–3026. https://doi.org/10.1038/emboj.2009.242
57. Yamaguchi N., Suzuki Y., Mahbub M. H., Takahashi H., Hase R., Ishimaru Y., Sunagawa H., Watanabe R., Eishi Y., TanabeT. The different roles of innate immune receptors in inflammation and carcinogenesis between races. Environmental Health and Preventive Medicine. 2017, V. 22. https://doi.org/10.1186/s12199-017-0678-8
58. Nagao S., Tanaka A., Yamamoto Y., Koga T., Onoue K., Shiba T., Kusumoto K., Kotani S. Inhibition of macrophage migration by muramyl peptides. Infect. Immun. 1979, 24 (2), 308–312. https://doi.org/10.1128/IAI.24.2.308-312.1979
59. Ogawa T., Kotani S., Fukuda K., Tsukamoto Y., Mori M., Kusumoto S., Shiba T. Stimulation of migration of human monocytes by bacterial cell walls and muramyl peptides. Infect. Immun. 1982, 38 (3), 817–824. https://doi.org/10.1128/IAI.38.3.817-824.1982
60. Sharma P., Karian J., Sharma S., Liu S., Mongan P. D. Pyruvate ameliorates post ischemic injury of rat astrocytes and protects them against PARP mediated cell death. Brain Res. 2003, 28, 992 (1), 104–113. https://doi.org/10.1016/j.brainres.2003.08.043
61. Phulwani N. K., Kielian T. Poly (ADP-ribose) polymerases (PARPs) 1-3 regulate astrocyte activation. J. Neurochem. 2008, 106 (2), 578–590. https://doi.org/10.1111/j.1471-4159.2008.05403.x
62. Kumar S., Ingle H., Prasad D. V. R., Kumar H. Recognition of bacterial infection by innate immune sensors. Critical Rev. Microbiol. 2013, V. 39, P. 229–246. https://doi.org/10.3109/1040841X.2012.706249
63. Royet J., Dziarski R. Peptidoglycan recognition proteins: Pleiotropic sensors and effectors of antimicrobial defences. Nat. Rev. Microbiol. 2007, V. 5, P. 264–277. https://doi.org/10.1038/nrmicro1620
64. Yang Y., Yin C., Pandey A., Abbott D., Sassetti C., Kelliher M. A. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J. Biol. Chem. 2007, 282, 36223–36229. https://doi.org/10.1074/jbc.M703079200 https://doi.org/10.1074/jbc.M703079200
65. Hasegawa M., Fujimoto Y., Lucas P. C., Nakano H., Fukase K., N??ez G., Inohara N. A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-?B activation. EMBO J. 2008, 27 (2), 373–383. https://doi.org/10.1038/sj.emboj.7601962
66. Kameoka M., Ota K., Tetsuka T., Tanaka Y., Itaya A., Okamoto T., Yoshihara K. Evidence for regulation of NF-kappaB by poly(ADP-ribose) polymerase. Biochem. J. 2000, 346 (3), 641–649. https://doi.org/10.1042/bj3460641
67. Hassa P. O., Hottiger M. O. The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-?B in inflammatory disorders. Cell. Molec. Life Sci. 2002, V. 59, P. 1534–1553. https://doi.org/10.1007/s00018-002-8527-2
68. Szab? C., Cuzzocrea S., Zingarelli B., O’Connor M., Salzman A. L. Endothelial dysfunction in a rat model of endotoxic shock: Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. J. Clin. Invest. 1997, 100 (3), 723–735. https://doi.org/10.1172/JCI119585
69. Saenz L., Lozano J. J., Valdor R., Baroja-Mazo A., Ramirez P., Parrilla P., Aparicio P., Sumoy L., Y?lamos J.Transcriptional regulation by Poly(ADP-ribose) polymerase-1 during T cell activation. BMC Genomics. 2008, 16 (9), 171. https://doi.org/10.1186/1471-2164-9-171
70. Nasta F., Laudisi F., Sambucci M., Rosado M. M., Pioli C. Increased Foxp3 + Regulatory T Cells in Poly(ADP-Ribose) Polymerase-1 Deficiency. J. Immunol. 2010, 1 (184), 3470–3477. https://doi.org/10.4049/jimmunol.0901568
71. Loeuillet C., Martinon F., Perez C., Munoz M., Thome M., Meylan P. R. Mycobacterium tuberculosis Subverts Innate Immunity to Evade Specific Effectors. J. Immunol. 2006, 177 (9), 6245–6255. https://doi.org/10.4049/jimmunol.177.9.6245
72. Deng W., Xie J. NOD2 Signaling and Role in Pathogenic Mycobacterium Recognition, Infection and Immunity. Cell. Physiol. Biochem. 2012, 30 (4), 953–963. https://doi.org/10.1159/000341472
73. Cavallari J. F., Barra N. G., Foley K. P., Lee A., Duggan B. M., Henriksbo B. D., Anh? F. F., Ashkar A. A., Schertzer J. D. Postbiotics for NOD2 require nonhematopoietic RIPK2 to improve blood glucose and metabolic inflammation in mice. Am. J. Physiol. Metab. 2020, 1, 318 (4), 579–585. https://doi.org/10.1152/ajpendo.00033.2020
74. McCarthy J. V., Ni J., Dixit V. M. RIP2 is a novel NF-?B-activating and cell death-inducing kinase. J. Biol. Chem. 1998, 273 (27), 16968–16975. https://doi.org/10.1074/jbc.273.27.16968
{/accordions}