Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2005; 51(6): 3-10

Allelic polymorphism of largemultifunctional proteases and itsfunctional meaning

V.E. Dosenko, D.A. Mikhalchuk, V.Yu. Zagoriy,N.V. Haitovich, A.A. Moibenko.

    O.O.Bogomoletz Institute of Physiology National Academy ofScience of Ukraine, KyivKyiv State University



Abstract

Proteasomal activity in isolated monocytes from subjects with different variants of large multifunctional proteases genes - LMP2 (Arg60 His allelic polymorphism) and LMP7 (Lys145 Gln allelic polymorphism) was determined. Trypsin-like activity of proteasome was 1.6-times (P=0.19) higher at Arg/Arg genotype comparing to His/His genotype, and 2-fold lower than at Arg/His genotype. The highest chymotrypsin-like activity of proteasome was observed in heterozygotes (on 29.7% higher comparing to Arg/Arg geno- type, Р=0.43) and lowest in homozygotes His/His (on 29.7% less comparing to Arg/Arg genotype, Р=0.40). Level of RNA expression in isolated monocytes detetermined by use of RT- PCR did not differed significantly in subjects with different genotypes. Data obtained indicate that LMP2 allelic poly- morphism impact peptidase activity of immunoproteasome.

Full text: (PDF, in Ukrainian)

References

  1. Cascio P., Hilton C., Kisselev A.F. et al. 26Sproteasomes and immunoproteasomes produce mainlyN-extended versions of an antigenic peptide // EMBOJ. – 2001. – 20, №10. – P.2357–2366.
  2. Craiu A., Akopian T., Goldberg A., Rock K.L. Twodistinct proteolytic processes in the generation of amajor histocompatibility complex class I-presentedpeptide // Proc. Natl. Acad. Sci. USA. – 1997. – 94,№20. – P.10850–10855.
  3. Deng G.Y., Muir A., Maclaren N.K., She J.X. Associa-tion of LMP2 and LMP7 genes within the major histo-compatibility complex with insulin-dependent diabe-tes mellitus: population and family studies // Amer. J.Hum. Genet. – 1995. – 56. – P.528–534.
  4. Dosenko V.E., Mikhalchyuk D.V., Moibenko A.A.Association between allelic variant of immunopro-teasome subunits (LMP2, LMP7) and acute coronarysyndrome // Abstracts of Joint 59th Harden EMBOConf. “The ubiquitin proteasome system in health anddisease” (Cirencester, 6–10 Sept., 2004). – P.15.
  5. Ehring B., Meyer T.H., Eckerskorn C. et al. Effects ofmajor–histocompatibility-complex-encoded subunitson the peptidase and proteolytic activities of human20S proteasomes. Cleavage of proteins and antigenicpeptides // Eur. J. Biochem. – 1996. – 235. – P.404–415.
  6. Gaczynska M., Goldberg A.L., Tanaka K. et al.Proteasome subunits X and Y alter peptidase activi-ties in opposite ways to the interferon-gamma-inducedsubunits LMP2 and LMP7 // J. Biol. Chem. – 1996. –271, №29. – P.17275–17280.
  7. Gaczynska M., Rock K.L., Spies T., Goldberg A.L.Peptidase activities of proteasomes are differentiallyregulated by the major histocompatibility complex-encoded genes for LMP2 and LMP7 // Proc. Natl. Acad.Sci. USA. – 1994. – 91, №20. – P.9213–9217.
  8. Goldberg A.L., Cascio P., Saric T., Rock K.L. Theimportance of the proteasome and subsequent pro-teolytic steps in the generation of antigenic peptides //Mol. Immunol. – 2002. – 39, №3–4. – P.147–164.
  9. 9. Kawaguchi Y., Ikegami H., Fukuda M. et al. Absenceof association of TAP and LMP genes with type 1(insulin-dependent) diabetes mellitus // Life Sci. – 1994. –54, №26. – P.2049–2053.
  10. 10. Kisselev A.F., Akopian T.N., Castillo V., Goldberg A.L.Proteasome active sites allosterically regulate each other,suggesting a cyclical bite-chew mechanism for proteinbreakdown // Mol. Cell. – 1999. – 4, №3. – P.395–402.
  11. Kisselev A.F., Garcia-Calvo M., Overkleeft H.S. et al.The caspase-like sites of proteasomes, their substratespecificity, new inhibitors and substrates, and allos-teric interactions with the trypsin-like sites // J. Biol.Chem. – 2003. – 278, №38. – P.35869–35877.
  12. Kisselev A.F., Kaganovich D., Goldberg A.L. Bindingof hydrophobic peptides to several non-catalytic sitespromotes peptide hydrolysis by all active sites of 20S proteasomes. Evidence for peptide-induced channelopening in the alpha-rings // Ibid. – 2002. – 277, №25. –P.22260–22270.
  13. Kuzushita N., Sugimoto Y., Sasaki Y., Hayashi N.Involvement of TAP2 and LMP7 gene polymorphismsin HCV infection // Nippon Rinsho. – 2001. – 59. –P.1248–1253.
  14. Li J., Schuler–Thurner B., Schuler G. et al. Bipartiteregulation of different components of the MHC class Iantigen-processing machinery during dendritic cellmaturation // Int. Immunol. – 2001. – 13, № 12. –P.1515–1523.
  15. Maksymowych W.P., Russell A.S. Polymorphism inthe LMP2 gene influences the relative risk for acuteanterior uveitis in unselected patients with ankylosingspondylitis // Clin. Invest. Med. – 1995. – 18. – P.42–46.
  16. Maksymowych W.P., Wessler A., Schmitt–Egenolf M.еt al. Polymorphism in an HLA linked proteasome geneinfluences phenotypic expression of disease in HLA-B27 positive individuals // J. Rheumatol. – 1994. – 21,№4. – P.665–669.
  17. Mishto M., Bonafe M., Salvioli S. et al. Age depen-dent impact of LMP polymorphisms on TNFalpha-induced apoptosis in human peripheral bloodmononuclear cells // Exp. Gerontol. – 2002. – 37, №2–3. – P.301–308.
  18. Mishto M., Bellavista E., Santoro A. et al. Immuno-proteasome and LMP2 codon 60 polymorphism in agedand Alzheimer’s disease brains // Abstracts of Joint59th Harden EMBO Conf. “The ubiquitin proteasomesystem in health and disease”і (Cirencester, 6–10 Sept.,2004). – P. 9.
  19. 19. Nagata N., Oshida T., Yoshida N.L. et al. Analysis ofhighly expressed genes in monocytes from atopicdermatitis patients // Int. Arch. Allergy Immunol. – 2003. –132, №2. – P.156–167.
  20. 20. Ovstebo R., Haug K.B.F., Lande K., Kierulf P. PCR-based calibration curves for studies of quantitative geneexpression in human monocytes: development and evalu-ation // Clin. Chem. – 2003. – 49, №3. – P.425–432.
  21. Pryhuber K.G., Murray K.J., Donnelly P. et al. Poly-morphism in the LMP2 gene influences disease sus-ceptibility and severity in HLA-B27 associated juve-nile rheumatoid arthritis // J. Rheumatol. – 1996. – 23. –P.747–752.
  22. van Endert P.M., Liblau R.S., Patel S.D. et al. Majorhistocompatibility complex-encoded antigen process-ing gene polymorphism in IDDM // Diabetes. – 1994. –43, №1. – P.110–117.
  23. Vinasco J., Fraile A., Nieto A. et al. Analysis of LMP andTAP polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in rheumatoidarthritis // Ann. Rheum. Dis. – 1998. – 57. – Р.33–37.
© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.