Role of granule proteins in lymphocyte‐mediated killing

Young, John Ding‐E; Cohn, Zanvil A.

doi:10.1002/jcb.240320207

Cited by 35 publications

(12 citation statements)

References 116 publications

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“…The commonly recognized mechanisms of lymphocyte cytotoxicity involve the following: (i) secretion of lymphokines that can exert cytotoxic effects like TNF␣ (46); (ii) exocytosis of cytolytic granules containing perforin and granzymes (47); and (iii) expression of the Fas ligand (FasL) on the effector cell surface (48). However, this clearly does not exhaust the possibilities of cytotoxic lymphocytes.…”

Section: Tag7-hsp70 Cytotoxic Complexmentioning

confidence: 99%

Peptidoglycan Recognition Protein Tag7 Forms a Cytotoxic Complex with Heat Shock Protein 70 in Solution and in Lymphocytes

Sashchenko

Dukhanina

Yashin

et al. 2004

Journal of Biological Chemistry

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The peptidoglycan recognition protein Tag7 is shown to form a stable 1:1 complex with the major stress protein Hsp70. Neither protein is cytotoxic by itself, but their complex induces apoptotic death in several tumorderived cell lines even at subnanomolar concentrations. The minimal part of Hsp70 needed to evoke cytotoxicity is residues 450 -463 of its peptide-binding domain, but full cytotoxicity requires its ATPase activity; remarkably, Tag7 liberated from the complex at high ATP is not cytotoxic. The Tag7-Hsp70 complex is produced by tag7-transfected cells and by lymphokine-activated killers, being assembled within the cell and released into the medium through the Golgi apparatus by a mechanism different from the commonly known granule exocytosis. Thus, we demonstrate how a heat shock protein may perform functions clearly distinct from chaperoning or cell rescue and how peptidoglycan recognition proteins may be involved in innate immunity and anti-cancer defense.

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Section: Tag7-hsp70 Cytotoxic Complexmentioning

confidence: 99%

Peptidoglycan Recognition Protein Tag7 Forms a Cytotoxic Complex with Heat Shock Protein 70 in Solution and in Lymphocytes

Sashchenko

Dukhanina

Yashin

et al. 2004

Journal of Biological Chemistry

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“…From morphologic analysis of CTL-target conjugates, Zagury (10) and the Henkarts (11) proposed that the lytic mechanism of CTL cells resided in their cytoplasmic "lysosome-like" granules, which move toward the particular bound target cell to be lysed following conjugation (12,13). Subsequently, several investigators (14)(15)(16)(17)(18)(19) have focused on analyzing the contents of these granules from CTL and NK cells. Several proteins have been isolated from the granules, including one that can reconstitute cytolytic activity, a protein termed cytolysin or perforin (20)(21)(22).…”

mentioning

confidence: 99%

Cloning and chromosomal assignment of a human cDNA encoding a T cell- and natural killer cell-specific trypsin-like serine protease.

Gershenfeld

Hershberger

Shows

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

105

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A cDNA clone encoding a human T cell-and natural killer cell-specific serine protease was obtained by screening a phage AgtlO cDNA library from phytohemagglutinin-stimulated human peripheral blood lymphocytes with the mouse Hanukah factor cDNA clone. In an RNA blothybridization analysis, this human Hanukah factor cDNA hybridized with a 1.3-kilobase band in allogeneic-stimulated cytotoxic T cells and the Jurkat cell line, but this transcript was not detectable in normal muscle, liver, tonsil, or thymus. By dot-blot hybridization, this cDNA hybridized with RNA from three cytolytic T-cell clones and three noncytolytic T-cell clones grown in vitro as well as with purified CD16' natural killer cells and CD3', CD16-T-cell large granular lymphocytes from peripheral blood lymphocytes (CD = cluster designation). The nucleotide sequence of this cDNA clone encodes a predicted serine protease of 262 amino acids. The predicted protein has a 22-amino acid presegment, a 6-amino acid prosegment, and an active enzyme of 234 amino acids with a calculated unglycosylated molecular weight of 25,820. The active enzyme is 71% and 77% similar to the mouse sequence at the amino acid and DNA level, respectively. The human apd mouse sequences conserve the active site residues of serine proteases-the trypsin-specific Asp-189 and all 10 cysteine residues. The gene for the human Hanukah factor serine protease is located on human chromosome 5. We propose that this trypsin-like serine protease may function as a common component necessary for lysis of target cells by cytotoxic T lymphocytes and natural killer cells.

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“…Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells form an integral component of cell-mediated immunity in humans, being responsible for the elimination of virusinfected cells and possibly providing immune surveillance for the detection of premalignant cells (1,2). One predominant model proposed for killing by both CTLs and NK cells involves the large, lysosome-like cytoplasmic granules prominent in both types of cell (3,4).…”

mentioning

confidence: 99%

Molecular cloning of an inducible serine esterase gene from human cytotoxic lymphocytes.

Trapani

Klein

White

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Role of granule proteins in lymphocyte‐mediated killing

Cited by 35 publications

References 116 publications

Peptidoglycan Recognition Protein Tag7 Forms a Cytotoxic Complex with Heat Shock Protein 70 in Solution and in Lymphocytes

Peptidoglycan Recognition Protein Tag7 Forms a Cytotoxic Complex with Heat Shock Protein 70 in Solution and in Lymphocytes

Cloning and chromosomal assignment of a human cDNA encoding a T cell- and natural killer cell-specific trypsin-like serine protease.

Molecular cloning of an inducible serine esterase gene from human cytotoxic lymphocytes.

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