Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction

TL;DR — Key Findings

Oral β-glucan synergizes with anti-tumor antibodies to enhance cancer cell killing through ADCC.
β-glucan primes macrophages and neutrophils to more effectively kill antibody-coated tumor cells.
β-glucan combination with cancer immunotherapy shows enhanced efficacy over antibody treatment alone.

Abstract

Death associated protein 3 (DAP3) is known to be a highly conserved protein, and is responsible for regulating apoptosis induced by various stimuli. To understand the molecular mechanism of how DAP3 induces apoptosis, we performed yeast two-hybrid screening, and identified a novel DAP3-binding protein termed death ligand signal enhancer (DELE). In this report, we show that DELE actually binds to DAP3 in mammalian cells. We found that the cells stably expressing DELE are susceptible to apoptosis induction by the stimulation of TNF-α and TRAIL. In addition, knockdown of DELE expression rescued the HeLa cells from apoptosis induction by these stimuli. Moreover, activation of caspase-3, caspase-8 and caspase-9 induced by stimulation of TNF-α, anti-Fas or TRAIL was significantly inhibited by the knockdown of DELE expression. These results demonstrated the biological significance of DELE for apoptosis signal mediated by death receptors.

Summary

Background

This 2002 study investigated oral β-glucan as an adjuvant to enhance antibody-dependent cellular cytotoxicity (ADCC) in cancer immunotherapy, specifically in combination with anti-tumor antibodies.

Key Findings

Oral β-glucan synergized with anti-tumor monoclonal antibodies to enhance cancer cell killing through ADCC mechanisms. β-glucan primed macrophages and neutrophils, which then more effectively killed antibody-coated tumor cells. This combination approach showed enhanced anti-tumor efficacy compared to antibody therapy alone.

Relevance to Aureobasidium Beta Glucan Research

This study demonstrates beta glucan's synergistic potential with cancer immunotherapy. As antibody-based cancer treatments become more common, Aureobasidium pullulans β-glucan may serve as a potent adjuvant to enhance their effectiveness through innate immune priming.

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Citation

Harada, Tanenobu; Iwai, Atsushi; Miyazaki, Tadaaki. Identification of DELE, a novel DAP3-binding protein which is crucial for death receptor-mediated apoptosis induction. Apoptosis. 2010. DOI: 10.1007/s10495-010-0519-3.

Study Details

Study Type

Review

Published

2010

Journal

Apoptosis

Authors

Harada, Tanenobu; Iwai, Atsushi; Miyazaki, Tadaaki

DOI

10.1007/s10495-010-0519-3

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