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Draft:MARCH1

From Wikipedia, the free encyclopedia


Membrane Associated Ring-CH 1 (MARCH1)[1], MARCH1 is an E3 ubiquitin ligase[2]. This type of enzyme is responsible for ubiquitination, a common process that causes endosomes to transport proteins to lysosomes for degradation[2][3]. It is observed to serve a role in both innate and adaptive immunity*. Primarily, through the regulation of Major Compatibility Complex (MHC) molecules class II and CD86[4][1] on antigen presenting cells' (APCs) surface. Both of these proteins are involved in the activation and development of T cells. [1]

Discovery

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MARCH1 was originally observed in herpes viruses as an immunoevasin[2]. K3 and K5 were seen in Kaposi's sarcoma associated herpes virus (KSHV) regulating MHC class I expression[1][5] . Since then 11 mammal homologs have been identified. MARCH 1 is most closely related to MARCH 8 in function and homology[1]. Not much is know about the other MARCH ligases, as MARCH 1 and 8 are the most researched for their involvement in immunity and potential clinical applications[6].

Structure

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All 11 MARCH ligases have a RING CH domain on the N terminus, and up to two transmembrane regions. MARCH1 specifically, is 298 amino acid residues long and contains two transmembrane regions[1]. The encoding gene is MARCHF1[7].

Immunological Roles

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Across various studies MARCH1 has been observed regulating key immunological molecules and cells, such as: MHC class II, and CD86[1][8][9]. MARCH1, along with 2,3,4, and 8, can reduce the binding abilities of immunoreceptors by increasing their turnover rate through lysosome activity or endocytosis[1]. Additionally, MARCH1, 2 and 8 can also reduce virulence by the same mechanisms removing viral envelopes on the cell surface[1].

MHC Class II

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A key function of the MARCH proteins is regulating the expression of MHC class II on the cells' surface. The location of ubiquitination is believed to be the cytoplasmic tail of the MHC class II molecule[1][10]. MARCH1 expression has been observed in mostly all the body's organs/tissues and on professional antigen presenting cells of hematopoietic descent, including: dendritic cells, B cells, macrophages, neutrophils, eosinophils, and monocytes[1][2].

CD86

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CD86 is a co-stimulatory molecule required to activate T cells and initiate an adaptive immune response.[11] It also plays a role in the development of T regulatory and NK T cells[8]. CD86's interaction with MARCH1 has not been researched as extensively. However, it is known that CD86 is ubiquitinated at lysine residue number 267 by MARCH1[11].

Regulation

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The expression of MHC class II and MARCH 1 are inversely related. When MARCH1 is around MHC class II is not recycled back to the cell's surface it is degraded. Alternatively, when the antigen presenting cell becomes activated MARCH1 is down regulated through TLR signaling and CD83 blocking its transmembrane domain to prevent ubiquitination of the MHC II molecules. Interestingly, in the absence of MARCH1 the expression of MHC class II on the cell membrane can increase between 5 to 10 times. Additionally, the half-life of MARCH1 is very short because it undergoes self-ubiquitination, maintaining low expression in all APCs. This has in turn made it difficult to identify other potential substrates of MARCH1[2][12]. IL-10 oppositely increases the transcription of MARCH1[1].

Additional Roles

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Experimental Findings

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  • In a study with MARCH1 deficient dendritic cells, TNF-alpha and IL-12 expression is reduced even with TLR stimulation [13] [14] [15]
  • Another study found that mice lacking the MARCH1 ligase had a more heighten inflammatory response producing more cytokines responding to LPS [16]
  • Conventional dendritic spleen cells from altered mice models show less surface MHC class II expression and less antigen presentation to CD8+ T cells [17]

References

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  1. ^ a b c d e f g h i j k l Liu, Haiyin; Mintern, Justine D; Villadangos, Jose A (2019-06-01). "MARCH ligases in immunity". Current Opinion in Immunology. Antigen processing • Special section on precommited lymphocytes. 58: 38–43. doi:10.1016/j.coi.2019.03.001. ISSN 0952-7915. PMID 31063934.
  2. ^ a b c d e Schriek, Patrick; Liu, Haiyin; Ching, Alan C.; Huang, Pauline; Gupta, Nishma; Wilson, Kayla R.; Tsai, MinHsuang; Yan, Yuting; Macri, Christophe F.; Dagley, Laura F.; Infusini, Giuseppe; Webb, Andrew I.; McWilliam, Hamish E.G.; Ishido, Satoshi; Mintern, Justine D. (2021). "Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8". Current Research in Immunology. 2: 218–228. doi:10.1016/j.crimmu.2021.10.004. ISSN 2590-2555. PMC 9040089. PMID 35492398.
  3. ^ Hershko, Avram; Ciechanover, Aaron (1998-07-01). "THE UBIQUITIN SYSTEM". Annual Review of Biochemistry. 67: 425–479. doi:10.1146/annurev.biochem.67.1.425. ISSN 0066-4154. PMID 9759494.
  4. ^ Schriek, Patrick; Liu, Haiyin; Ching, Alan C.; Huang, Pauline; Gupta, Nishma; Wilson, Kayla R.; Tsai, MinHsuang; Yan, Yuting; Macri, Christophe F.; Dagley, Laura F.; Infusini, Giuseppe; Webb, Andrew I.; McWilliam, Hamish E. G.; Ishido, Satoshi; Mintern, Justine D. (2021-01-01). "Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8". Current Research in Immunology. 2: 218–228. doi:10.1016/j.crimmu.2021.10.004. ISSN 2590-2555. PMC 9040089. PMID 35492398.
  5. ^ Ishido, Satoshi; Wang, Chunyang; Lee, Bok-Soo; Cohen, George B.; Jung, J. U. (June 2000). "Downregulation of Major Histocompatibility Complex Class I Molecules by Kaposi's Sarcoma-Associated Herpesvirus K3 and K5 Proteins". Journal of Virology. 74 (11): 5300–5309. doi:10.1128/JVI.74.11.5300-5309.2000. ISSN 0022-538X. PMC 110885. PMID 10799607.
  6. ^ Kishta, Osama A.; Sabourin, Antoine; Simon, Leora; McGovern, Toby; Raymond, Maxime; Galbas, Tristan; Majdoubi, Abdelilah; Ishido, Satoshi; Martin, James G.; Thibodeau, Jacques (2018). "March1 E3 Ubiquitin Ligase Modulates Features of Allergic Asthma in an Ovalbumin-Induced Mouse Model of Lung Inflammation". Journal of Immunology Research. 2018 (1) 3823910. doi:10.1155/2018/3823910. ISSN 2314-7156. PMC 5960577. PMID 29854835.
  7. ^ "MARCHF1 membrane associated ring-CH-type finger 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2026-07-24.
  8. ^ a b Oh, Jaehak; Wu, Nan; Baravalle, Günther; Cohn, Benjamin; Ma, Jessica; Lo, Bryan; Mellman, Ira; Ishido, Satoshi; Anderson, Mark; Shin, Jeoung-Sook (2013-05-27). "MARCH1-mediated MHCII ubiquitination promotes dendritic cell selection of natural regulatory T cells". Journal of Experimental Medicine. 210 (6): 1069–1077. doi:10.1084/jem.20122695. ISSN 0022-1007. PMC 3674695. PMID 23712430.
  9. ^ Baravalle, Günther; Park, Hyesuk; McSweeney, Megan; Ohmura-Hoshino, Mari; Matsuki, Yohei; Ishido, Satoshi; Shin, Jeoung-Sook (2011-09-15). "Ubiquitination of CD86 Is a Key Mechanism in Regulating Antigen Presentation by Dendritic Cells". The Journal of Immunology. 187 (6): 2966–2973. doi:10.4049/jimmunol.1101643. ISSN 0022-1767. PMC 4496154. PMID 21849678.
  10. ^ Matsuki, Yohei; Ohmura-Hoshino, Mari; Goto, Eiji; Aoki, Masami; Mito-Yoshida, Mari; Uematsu, Mika; Hasegawa, Takanori; Koseki, Haruhiko; Ohara, Osamu; Nakayama, Manabu; Toyooka, Kiminori; Matsuoka, Ken; Hotta, Hak; Yamamoto, Akitsugu; Ishido, Satoshi (2007-02-01). "Novel regulation of MHC class II function in B cells". The EMBO Journal. 26 (3): 846–854. doi:10.1038/sj.emboj.7601556. ISSN 1460-2075. PMC 1794403. PMID 17255932.
  11. ^ a b Baravalle, Günther; Park, Hyesuk; McSweeney, Megan; Ohmura-Hoshino, Mari; Matsuki, Yohei; Ishido, Satoshi; Shin, Jeoung-Sook (2011-09-01). "Ubiquitination of CD86 Is a Key Mechanism in Regulating Antigen Presentation by Dendritic Cells". The Journal of Immunology. 187 (6): 2966–2973. doi:10.4049/jimmunol.1101643. ISSN 0022-1767. PMC 4496154. PMID 21849678.
  12. ^ Eyster, Craig A.; Cole, Nelson B.; Petersen, Shariska; Viswanathan, Kasinath; Fr, üh Klaus; Donaldson, Julie G.; Gruenberg, Jean E. (September 2011). "MARCH ubiquitin ligases alter the itinerary of clathrin-independent cargo from recycling to degradation". Molecular Biology of the Cell. 22 (17): 3218–3230. doi:10.1091/mbc.e10-11-0874. PMC 3164467. PMID 21757542.
  13. ^ Ohmura-Hoshino, Mari; Matsuki, Yohei; Mito-Yoshida, Mari; Goto, Eiji; Aoki-Kawasumi, Masami; Nakayama, Manabu; Ohara, Osamu; Ishido, Satoshi (2009-12-01). "Cutting Edge: Requirement of MARCH-I-Mediated MHC II Ubiquitination for the Maintenance of Conventional Dendritic Cells". The Journal of Immunology. 183 (11): 6893–6897. doi:10.4049/jimmunol.0902178. ISSN 0022-1767. PMID 19917682.
  14. ^ Bourgeois-Daigneault, Marie-Claude; Pezeshki, Abdul Mohammad; Galbas, Tristan; Houde, Mathieu; Baril, Martin; Früh, Klaus; Amrani, Abdelaziz; Ishido, Satoshi; Lamarre, Daniel; Thibodeau, Jacques (2013-01-01). "Tollip-induced down-regulation of MARCH1". Results in Immunology. 3: 17–25. doi:10.1016/j.rinim.2013.02.002. ISSN 2211-2839. PMC 3908327. PMID 24600555.
  15. ^ Ishikawa, Rikiya; Kajikawa, Mizuho; Ishido, Satoshi (2014-05-01). "Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells". International Immunology. 26 (5): 283–289. doi:10.1093/intimm/dxt066. ISSN 1460-2377. PMID 24370470.
  16. ^ Galbas, Tristan; Raymond, Maxime; Sabourin, Antoine; Bourgeois-Daigneault, Marie-Claude; Guimont-Desrochers, Fanny; Yun, Tae Jin; Cailhier, Jean-François; Ishido, Satoshi; Lesage, Sylvie; Cheong, Cheolho; Thibodeau, Jacques (2017-01-15). "MARCH1 E3 Ubiquitin Ligase Dampens the Innate Inflammatory Response by Modulating Monocyte Functions in Mice". The Journal of Immunology. 198 (2): 852–861. doi:10.4049/jimmunol.1601168. ISSN 0022-1767. PMID 27940660.
  17. ^ Wilson, Kayla R.; Liu, Haiyin; Healey, Geraldine; Vuong, Vivian; Ishido, Satoshi; Herold, Marco J.; Villadangos, Jose A.; Mintern, Justine D. (2018-07-12). "MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway". PLOS ONE. 13 (7) e0200540. Bibcode:2018PLoSO..1300540W. doi:10.1371/journal.pone.0200540. ISSN 1932-6203. PMC 6042767. PMID 30001419.
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