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SADS: A new component of Fas-DISC is the accelerator for cell death signaling and is downregulated in patients with colon carcinoma

Nature Medicine volume 7, pages 88–93 (2001)Cite this article

A Retraction to this article was published on 01 June 2001

Abstract

Fas is the death receptor, transducing cell death signaling upon stimulation by Fas ligand. During Fas-initiated cell death signaling, the formation of Fas-death inducing signaling complex (Fas-DISC) is the first step. Here we have identified a new component of Fas-DISC which we call 'small-accelerator for death signaling' (SADS). SADS cDNA encodes a 150 amino acid polypeptide (Mr = 16,700). During Fas-mediated cell death, SADS enhances the interaction of Fas-death domain-interactive factors (FADD) and procaspase-8, and deletion mutant analysis has identified FADD- and caspase-8-interactive domains in SADS. Inhibition or removal of SADS delays Fas-mediated cell death. In addition, we demonstrate the deletion or mutation of SADS in patients with colon carcinoma and that exogenous SADS expression in human colon carcinoma SW480 cells that lack SADS leads to re-acquisition of Fas-mediated cell death. Here, we propose that SADS is one of the cell death-associated factors and enhances Fas-DISC formation, especially FADD and procaspase-8 recruitment.

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Figure 1: a, Fas-DISC from Jurkat cells.
Figure 2: a, Expression vector with or without (M) SADS was transfected in D98AH2 cells at a concentration of 5 μg (H) or 1 μg (L) expression vector DNA.
Figure 3: Effect of SADS antisense vector.
Figure 4: Effect of SADS mutants.
Figure 5: Effect of SADS in type-I or type-II Fas-mediated cell death.
Figure 6: SADS in colon carcinoma.

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Acknowledgements

We thank S. Sugano for the KATO8558 cDNA clone in pME18S-FL; Y. Tsujimoto for D98AH2 cell line; S. Yonehara for human caspase-8 expression vector; M. Miura and Y. Gotoh for discussions; and K. Akahane, M. Aonuma and Y. Kita for technical suggestions.

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Authors and Affiliations

  1. Project for the Cell Death Research, Basic Technology Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center, Kitakasai 1-16-13, Edogawa-ku, 134-8630, Tokyo, Japan

    Atsushi Suzuki, Midori Hayashida & Hirokazu Kawano

  2. Biochemical Laboratory, Research & Development Group, Kishida Chemical Co., Ltd., Sanda Factory, Techno-Park 14-10, Sanda, 669-1339, Hyogo, Japan

    Shigehiro Obata

  3. The First Department of Internal Medicine, Mie University School of Medicine, Edobashi 2-174, Tsu, 514-8507, Mie, Japan

    Takeshi Nakano & Katsuya Shiraki

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  1. Atsushi Suzuki
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Correspondence to Atsushi Suzuki.

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Suzuki, A., Obata, S., Hayashida, M. et al. SADS: A new component of Fas-DISC is the accelerator for cell death signaling and is downregulated in patients with colon carcinoma. Nat Med 7, 88–93 (2001). https://doi.org/10.1038/83401

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