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Perforin-1

Definition:

Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells. Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g. in transplant rejection or some forms of autoimmune disease. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes. Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes. Perforin pores allow the release of mature caspase-7 (CASP7) into the extracellular milieu (By similarity).

References:

[1]. Tilen Praper, et al. Human perforin employs different avenues to damage membranes. J Biol Chem. 2011 Jan 28;286(4):2946-55. [Content Brief]

[2]. Ruby H P Law, et al. The structural basis for membrane binding and pore formation by lymphocyte perforin. Nature. 2010 Nov 18;468(7322):447-51. [Content Brief]

[3]. Zhiwei Zhou, et al. Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science. 2020 May 29;368(6494):eaaz7548. [Content Brief]

[4]. M Vergelli, et al. Human autoreactive CD4+ T cell clones use perforin- or Fas/Fas ligand-mediated pathways for target cell lysis. J Immunol. 1997 Mar 15;158(6):2756-61. [Content Brief]

[5]. K Ando, et al. Perforin, Fas/Fas ligand, and TNF-alpha pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL. J Immunol. 1997 Jun 1;158(11):5283-91. [Content Brief]

[6]. Malgorzata Czystowska, et al. Reciprocal granzyme/perforin-mediated death of human regulatory and responder T cells is regulated by interleukin-2 (IL-2). J Mol Med (Berl). 2010 Jun;88(6):577-88. [Content Brief]

[7]. Jerome Thiery, et al. Perforin activates clathrin- and dynamin-dependent endocytosis, which is required for plasma membrane repair and delivery of granzyme B for granzyme-mediated apoptosis. Blood. 2010 Feb 25;115(8):1582-93. [Content Brief]

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