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Gene Review

Prf1  -  perforin 1 (pore forming protein)

Mus musculus

Synonyms: Cytolysin, Lymphocyte pore-forming protein, P1, Perforin-1, Pfn, ...
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Disease relevance of Prf1


Psychiatry related information on Prf1


High impact information on Prf1


Chemical compound and disease context of Prf1


Biological context of Prf1


Anatomical context of Prf1

  • This distinction in outcome depended on accumulation of mononuclear cells and T cells in infected Prf1(-/-) mice [1].
  • We have tested the use of NOD- Rag1 null Prf1 null mice as recipients in a long-term xenograft assay for human hematopoietic stem cells (HSCs) by adopting Yoder and colleagues' method of conditioned newborn mice, with minor modifications [22].
  • Transfer of perforin-competent NK cells restores the ability of PKO mice to clonally expand CD8 CTL in response to gp96-Ig [23].
  • Thus, perforin-dependent cytotoxicity is not only a crucial mechanism of both cytotoxic T lymphocyte- and NK-dependent resistance to injected tumor cell lines, but also operates during viral and chemical carcinogenesis in vivo [24].
  • RESULTS: Colon cytotoxic T lymphocyte displayed both Fas- and perforin-dependent killing [4].

Associations of Prf1 with chemical compounds

  • Pregnant NOD- Rag1 null Prf1 null dams were treated with busulfan 22.5 mg/kg [22].
  • Perforin has been located in all of the granules, whereas gold particles corresponding to serine esterases have been found in most of the granules [17].
  • The cytotoxicity was dose-dependently inhibited by either a Con A ligand, alpha-methyl mannoside, or a perforin inhibitor, concanamycin A (CMA), but not by anti-Fas ligand antiserum [25].
  • On the other hand, the cytotoxic activity of AIM against the allografts was dose dependently inhibited by EGTA; and the suppression was restored by the addition of Ca2+, but not Mg2+, implying the involvement of perforin in the cytotoxicity [26].
  • In contrast, brefeldin A blocked the Fas-based cytotoxicity, but only marginally reduced the perforin-based cytotoxicity [27].

Physical interactions of Prf1


Enzymatic interactions of Prf1

  • Perforin adsorbed to resistant cells was cleaved by trypsin into a 55-kDa (C-terminal) and a 10- to 15-kDa (N-terminal) fragment, whereas this cleavage was not found on tumor cell-bound perforin [30].

Co-localisations of Prf1

  • In PM and IBM, PF positive cells were colocalized with GA positive cells and occasionally invaded into the non-necrotic muscle fibres [31].

Regulatory relationships of Prf1


Other interactions of Prf1

  • Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways [2].
  • Here we report that both perforin-deficient and Fas-ligand-deficient CTLs show impaired lytic activity on all target cells tested [2].
  • We evaluated the development of spontaneous tumors in mice lacking beta-2 microglobulin (beta2m; and thus MHC class I, CD1d, and CD16) and/or perforin, since these tumor cells would be expected to activate innate effector cells [3].
  • Granzyme B-independent cytotoxicity is therefore partially accounted for by the Fas pathway and partially by another perforin-dependent mechanism [36].
  • Moreover, SPI-CI can protect cells from purified perforin/GrM-induced lysis [37].

Analytical, diagnostic and therapeutic context of Prf1


  1. Perforin and granzymes have distinct roles in defensive immunity and immunopathology. van Dommelen, S.L., Sumaria, N., Schreiber, R.D., Scalzo, A.A., Smyth, M.J., Degli-Esposti, M.A. Immunity (2006) [Pubmed]
  2. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Lowin, B., Hahne, M., Mattmann, C., Tschopp, J. Nature (1994) [Pubmed]
  3. Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cells. Street, S.E., Hayakawa, Y., Zhan, Y., Lew, A.M., MacGregor, D., Jamieson, A.M., Diefenbach, A., Yagita, H., Godfrey, D.I., Smyth, M.J. J. Exp. Med. (2004) [Pubmed]
  4. Consequences of Fas-ligand and perforin expression by colon T cells in a mouse model of inflammatory bowel disease. Simpson, S.J., De Jong, Y.P., Shah, S.A., Comiskey, M., Wang, B., Spielman, J.A., Podack, E.R., Mizoguchi, E., Bhan, A.K., Terhorst, C. Gastroenterology (1998) [Pubmed]
  5. Modulation of perforin, granzyme A, and granzyme B in murine natural killer (NK), IL2 stimulated NK, and lymphokine-activated killer cells by alcohol consumption. Spitzer, J.H., Meadows, G.G. Cell. Immunol. (1999) [Pubmed]
  6. Effect of electric foot shock and psychological stress on activities of murine splenic natural killer and lymphokine-activated killer cells, cytotoxic T lymphocytes, natural killer receptors and mRNA transcripts for granzymes and perforin. Li, Q., Liang, Z., Nakadai, A., Kawada, T. Stress (Amsterdam, Netherlands) (2005) [Pubmed]
  7. Local immune responses to influenza virus infection in mice with a targeted disruption of perforin gene. Liu, B., Mori, I., Hossain, M.J., Dong, L., Chen, Z., Kimura, Y. Microb. Pathog. (2003) [Pubmed]
  8. Induction of the immune response to Legionella pneumophila cytolysin by monoclonal anti-idiotypic antibodies. Spitsin, S.V., Drobyshevskaya, E.I., Barkhatova, O.I., Belyi, Y.F., Tartakovsky, I.S., Nesterenko, V.G. J. Immunol. (1991) [Pubmed]
  9. Lymphocyte-mediated cytotoxicity. Russell, J.H., Ley, T.J. Annu. Rev. Immunol. (2002) [Pubmed]
  10. CD8+ T cell effector mechanisms in resistance to infection. Harty, J.T., Tvinnereim, A.R., White, D.W. Annu. Rev. Immunol. (2000) [Pubmed]
  11. Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. Kägi, D., Ledermann, B., Bürki, K., Zinkernagel, R.M., Hengartner, H. Annu. Rev. Immunol. (1996) [Pubmed]
  12. Cutting edge: novel priming of tumor-specific immunity by NKG2D-triggered NK cell-mediated tumor rejection and Th1-independent CD4+ T cell pathway. Westwood, J.A., Kelly, J.M., Tanner, J.E., Kershaw, M.H., Smyth, M.J., Hayakawa, Y. J. Immunol. (2004) [Pubmed]
  13. Seeligeriolysin O, a cholesterol-dependent cytolysin of Listeria seeligeri, induces gamma interferon from spleen cells of mice. Ito, Y., Kawamura, I., Kohda, C., Baba, H., Nomura, T., Kimoto, T., Watanabe, I., Mitsuyama, M. Infect. Immun. (2003) [Pubmed]
  14. Homeostatic regulation of CD8+ T cells by perforin. Kägi, D., Odermatt, B., Mak, T.W. Eur. J. Immunol. (1999) [Pubmed]
  15. The perforin mediated apoptotic pathway in lung injury and fibrosis. Miyazaki, H., Kuwano, K., Yoshida, K., Maeyama, T., Yoshimi, M., Fujita, M., Hagimoto, N., Yoshida, R., Nakanishi, Y. J. Clin. Pathol. (2004) [Pubmed]
  16. Perforin mRNA expression in the inflamed tissues of NZB/W F1 lupus mice decreases with methylprednisolone treatment. Nakamura, T., Ebihara, I., Tomino, Y., Okumura, K., Koide, H. Am. J. Pathol. (1991) [Pubmed]
  17. Immunogold labeling of perforin and serine esterases in granulated metrial gland cells. Zheng, L.M., Ojcius, D.M., Liu, C.C., Kramer, M.D., Simon, M.M., Parr, E.L., Young, J.D. FASEB J. (1991) [Pubmed]
  18. Perforin-dependent neurologic injury in a viral model of multiple sclerosis. Murray, P.D., McGavern, D.B., Lin, X., Njenga, M.K., Leibowitz, J., Pease, L.R., Rodriguez, M. J. Neurosci. (1998) [Pubmed]
  19. Fas ligand (CD95L) protects neurons against perforin-mediated T lymphocyte cytotoxicity. Medana, I., Li, Z., Flügel, A., Tschopp, J., Wekerle, H., Neumann, H. J. Immunol. (2001) [Pubmed]
  20. Inhibition of CTL induction by rapamycin: IL-2 rescues granzyme B and perforin expression but only partially restores cytotoxic activity. Makrigiannis, A.P., Hoskin, D.W. J. Immunol. (1997) [Pubmed]
  21. IL-1 beta convertase (ICE) does not play a requisite role in apoptosis induced in T lymphoblasts by Fas-dependent or Fas-independent CTL effector mechanisms. Smith, D.J., McGuire, M.J., Tocci, M.J., Thiele, D.L. J. Immunol. (1997) [Pubmed]
  22. An assay for human hematopoietic stem cells based on transplantation into nonobese diabetic recombination activating gene-null perforin-null mice. Minamiguchi, H., Wingard, J.R., Laver, J.H., Mainali, E.S., Shultz, L.D., Ogawa, M. Biol. Blood Marrow Transplant. (2005) [Pubmed]
  23. Perforin is required for innate and adaptive immunity induced by heat shock protein gp96. Strbo, N., Oizumi, S., Sotosek-Tokmadzic, V., Podack, E.R. Immunity (2003) [Pubmed]
  24. Decreased tumor surveillance in perforin-deficient mice. van den Broek, M.E., Kägi, D., Ossendorp, F., Toes, R., Vamvakas, S., Lutz, W.K., Melief, C.J., Zinkernagel, R.M., Hengartner, H. J. Exp. Med. (1996) [Pubmed]
  25. Concanavalin A induces perforin-mediated but not Fas-mediated hepatic injury. Watanabe, Y., Morita, M., Akaike, T. Hepatology (1996) [Pubmed]
  26. Ca2+-dependent, Fas- and perforin-independent apoptotic death of allografted tumor cells by a type of activated macrophage. Yoshida, R., Sanchez-Bueno, A., Yamamoto, N., Einaga-Naito, K. J. Immunol. (1997) [Pubmed]
  27. Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity. Kataoka, T., Shinohara, N., Takayama, H., Takaku, K., Kondo, S., Yonehara, S., Nagai, K. J. Immunol. (1996) [Pubmed]
  28. Type II pneumocyte-CD8+ T-cell interactions. Relationship between target cell cytotoxicity and activation. Zhao, M.Q., Amir, M.K., Rice, W.R., Enelow, R.I. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  29. Hemolytic mechanism of cytolysin produced from V. vulnificus. Kim, H.R., Rho, H.W., Jeong, M.H., Park, J.W., Kim, J.S., Park, B.H., Kim, U.H., Park, S.D. Life Sci. (1993) [Pubmed]
  30. Resistance of CTL to perforin-mediated lysis. Evidence for a lymphocyte membrane protein interacting with perforin. Müller, C., Tschopp, J. J. Immunol. (1994) [Pubmed]
  31. Immunohistochemical analysis of perforin and granzyme A in inflammatory myopathies. Orimo, S., Koga, R., Goto, K., Nakamura, K., Arai, M., Tamaki, M., Sugita, H., Nonaka, I., Arahata, K. Neuromuscul. Disord. (1994) [Pubmed]
  32. Bcl-2 prevents apoptosis induced by perforin and granzyme B, but not that mediated by whole cytotoxic lymphocytes. Sutton, V.R., Vaux, D.L., Trapani, J.A. J. Immunol. (1997) [Pubmed]
  33. Perforin and Fas act together in the induction of apoptosis, and both are critical in the clearance of lymphocytic choriomeningitis virus infection. Rode, M., Balkow, S., Sobek, V., Brehm, R., Martin, P., Kersten, A., Dumrese, T., Stehle, T., Müllbacher, A., Wallich, R., Simon, M.M. J. Virol. (2004) [Pubmed]
  34. Perforin-dependent activation-induced cell death acts through caspase 3 but not through caspases 8 or 9. Chen, L., Woo, M., Hakem, R., Miller, R.G. Eur. J. Immunol. (2003) [Pubmed]
  35. IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-gamma. Ma, H.L., Whitters, M.J., Konz, R.F., Senices, M., Young, D.A., Grusby, M.J., Collins, M., Dunussi-Joannopoulos, K. J. Immunol. (2003) [Pubmed]
  36. Mechanisms responsible for granzyme B-independent cytotoxicity. Shresta, S., Russell, J.H., Ley, T.J. Blood (1997) [Pubmed]
  37. SPI-CI and SPI-6 cooperate in the protection from effector cell-mediated cytotoxicity. Bots, M., Kolfschoten, I.G., Bres, S.A., Rademaker, M.T., de Roo, G.M., Krüse, M., Franken, K.L., Hahne, M., Froelich, C.J., Melief, C.J., Offringa, R., Medema, J.P. Blood (2005) [Pubmed]
  38. Both perforin and Fas ligand are required for the regulation of alloreactive CD8+ T cells during acute graft-versus-host disease. Maeda, Y., Levy, R.B., Reddy, P., Liu, C., Clouthier, S.G., Teshima, T., Ferrara, J.L. Blood (2005) [Pubmed]
  39. Tumor regression after adoptive transfer of effector T cells is independent of perforin or Fas ligand (APO-1L/CD95L). Winter, H., Hu, H.M., Urba, W.J., Fox, B.A. J. Immunol. (1999) [Pubmed]
  40. Morphologic and functional characterization of perforin-deficient lymphokine-activated killer cells. Liu, C.C., Walsh, C.M., Eto, N., Clark, W.R., Young, J.D. J. Immunol. (1995) [Pubmed]
  41. Cytotoxic T lymphocyte-assisted suicide. Caspase 3 activation is primarily the result of the direct action of granzyme B. Atkinson, E.A., Barry, M., Darmon, A.J., Shostak, I., Turner, P.C., Moyer, R.W., Bleackley, R.C. J. Biol. Chem. (1998) [Pubmed]
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