Human CD59 is a receptor for the cholesterol-dependent cytolysin intermedilysin

Giddings, Kara S.; Zhao, Jinmin; Sims, P.; Tweten, Rodney K.

doi:10.1038/nsmb862

Cited by 210 publications

(270 citation statements)

References 39 publications

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“…Domain 4 also participates in the binding of hCD59 to C8a and C9. 30,33 We have consistently demonstrated that rILYd4 specifically abrogates hCD59 function in both normal human cells and B lymphoma cells. Furthermore, we demonstrated that rILYd4 (IC 50 533 nM) restores the sensitivity of a rituximabresistant NHL cell line to the rituximab CDC effect.…”

Section: Introductionmentioning

confidence: 86%

“…The receptor for ILY is specific for hCD59. 30,31 Using the generation of different mutant ILYs, LaChapelle et al recently demonstrated that the ILY-hCD59 interaction during the assembly of the pore complex increases host cell susceptibility to the CDC effect. 32 Domains 1-3 of ILY are responsible for pore formation, while domain 4 binds to amino acids 42-58 in hCD59.…”

Section: Introductionmentioning

confidence: 99%

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Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells

You

et al. 2011

Cell Mol Immunol

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Many monoclonal antibodies (mAbs) have been extensively used in the clinic, such as rituximab to treat lymphoma. However, resistance and non-responsiveness to mAb treatment have been challenging for this line of therapy. Complement is one of the main mediators of antibody-based cancer therapy via the complement-dependent cytolysis (CDC) effect. CD59 plays a critical role in resistance to mAbs through the CDC effect. In this paper, we attempted to investigate whether the novel CD59 inhibitor, recombinant ILYd4, was effective in enhancing the rituximab-mediated CDC effect on rituximab-sensitive RL-7 lymphoma cells and rituximab-induced resistant RR51.2 cells. Meanwhile, the CDC effects, which were mediated by rituximab and anti-CD24 mAb, on the refractory multiple myeloma (MM) cell line ARH-77 and the solid tumor osteosarcoma cell line Saos-2, were respectively investigated. We found that rILYd4 rendered the refractory cells sensitive to the mAb-mediated CDC effect and that rILYd4 exhibited a synergistic effect with the mAb that resulted in tumor cells lysis. This effect on tumor cell lysis was apparent on both hematological tumors and solid tumors. Therefore, rILYd4 may serve as an adjuvant for mAb mediated-tumor immunotherapy. Keywords: CD59; complement; lymphoma; multiple myeloma; rituximab INTRODUCTIONMonoclonal antibody (mAb) therapy is becoming a powerful approach and is increasingly used in the clinic for the treatment of different types of cancer through targeting specific cancer antigens. Rituximab, the first mAb approved for cancer therapy by the Food and Drug Administration, has been successfully used in the treatment of B-cell non-Hodgkin's B-lymphoma (NHL) via specifically targeting the CD20 molecule on the B lymphocyte membrane. Treatment with rituximab has lead to greatly improved clinical outcomes. 1 Trastuzumab (Herceptin) is used to treat HER2-positive breast cancer. Other new mAbs are actively being developed. Once the antibodies (Abs) are given, they can then recruit other parts of the immune system to destroy the cancer cells or to enhance the immune response against the cancer. The mechanism of action of these Abs and the host and cellular factors that influence the immune response following Ab treatment are not completely known. The induction of apoptosis, Abdependent cell cytotoxicity and complement-mediated cell death (CDC) are the proposed mechanisms of action of these Abs. 2 Complement is one of the main mediators of Ab-based cancer therapy via the CDC effect. When cancer therapeutic Abs activate the so-called classical complement pathway, they trigger the formation of the membrane attack complex on cancer cells, leading to the killing of cancer cells through CDC. 3 CD59, a critical membrane complement regulator, inhibits membrane attack complex formation by binding to

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Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells

You

et al. 2011

Cell Mol Immunol

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“…This is often achieved by one or more mechanisms such as regulated secretion (perforin), 3 proteolytic activation (perforin), 3 pH sensitivity (LLO, perforin), 3,25 receptor specificity to target membranes (intermedilysin) 36 or the presence of immunity proteins on non-target membranes (complement MAC). 37 How apicomplexan parasites prevent autolysis by ApiPLPs following secretion remains an interesting area deserving of additional work.…”

Section: Discussionmentioning

confidence: 99%

Apicomplexan perforin-like proteins

Kafsack

Carruthers

2010

Communicative & Integrative Biology

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“…A good example is the intermedilysin (ILY) of Streptococcus intermedius which recognises CD59, an GPI-anchored protein, as the membrane receptor although it has been classified as a cholesterol-dependent cytolysin (Giddings et al 2004). a-hemolysin of In summary, by a combination of affinity purification and SILAC-based quantitative mass spectrometry we have identified the folate receptor alpha as an interaction partner of HALT-1.…”

Section: Discussionmentioning

confidence: 99%

“…A few bacterial pore-forming toxins have been proven to bind proteinaceous receptors in addition of their affinity to membrane lipids (Dal Peraro and van der Goot 2016; DuMont and Torres 2014). These pore-forming toxins include the intermedilysin (ILY) of Streptococcus intermedius which recognises CD59, an GPI-anchored protein, as the membrane receptor although it has been classified as a cholesterol-dependent cytolysin (Giddings et al 2004). Hence, membrane proteins can be potential candidates as receptors for HALT-1.…”

Section: Introductionmentioning

confidence: 99%

Identification of a target protein of Hydra actinoporin-like toxin-1 (HALT-1) using GST affinity purification and SILAC-based quantitative proteomics

Ameirika

Hong

Hwang

2017

Toxicon

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Hydra actinoporin-like toxin-1 (HALT-1) is a 20.8 kDa pore-forming toxin isolated from Hydra magnipapillata. HALT-1 shares structural similarity with actinoporins, a family that is well known for its haemolytic and cytolytic activity. However, the precise pore-forming mechanism of HALT-1 remains an open question since little is known about the specific target binding for HALT-1. For this reason, a comprehensive proteomic analysis was performed using affinity purification and SILAC-based mass spectrometry to identify potential protein-protein interactions between mammalian HeLa cell surface proteins and HALT-1. A total of 4 mammalian proteins was identified, of which only folate receptor alpha was further verified by ELISA. Our preliminary results highlight an alternative-binding mode of HALT-1 to the human plasma membrane. This is the first evidence showing that HALT-1, an actinoporin-like protein, binds to a membrane protein, the folate receptor alpha. This study would advance our understanding of the molecular basis of toxicity of pore-forming toxins and provide new insights in the production of more potent inhibitors for the toxin-membrane receptor interactions.3

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Human CD59 is a receptor for the cholesterol-dependent cytolysin intermedilysin

Cited by 210 publications

References 39 publications

Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells

Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells

Apicomplexan perforin-like proteins

Identification of a target protein of Hydra actinoporin-like toxin-1 (HALT-1) using GST affinity purification and SILAC-based quantitative proteomics

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