Journal Article

ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia cells

Junichi Matsuzaki, Toshihiko Torigoe, Yoshihiko Hirohashi, Kenjiro Kamiguchi, Yasuaki Tamura, Tomohide Tsukahara, Terufumi Kubo, Akari Takahashi, Emiri Nakazawa, Eri Saka, Kazuyo Yasuda, Shuji Takahashi and Noriyuki Sato

in Carcinogenesis

Volume 33, issue 5, pages 996-1003
Published in print May 2012 | ISSN: 0143-3334
Published online March 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs118
ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia cells

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We previously established Fas-resistant variant clones from the human T-cell leukemia lines Jurkat and SUP-T13. Comparative gene expression analysis of the Fas-resistant and Fas-sensitive clones revealed several genes that were aberrantly expressed in the Fas-resistant clones. One of the genes, esophageal cancer-related gene 4 (ECRG4), contained a VDAC2-like domain that might be associated with apoptotic signals. In the present study, we examined the subcellular localization and function of ECRG4 in Fas-mediated apoptosis. By confocal fluorescence microscopy, ECRG4-EGFP fusion protein was detected in mitochondria, endoplasmic reticulum and the Golgi apparatus in gene-transfected HeLa cells. Overexpression of ECRG4 in Fas-sensitive Jurkat cells inhibited mitochondrial membrane permeability transition, leading to resistance against Fas-induced apoptosis. Tumor necrosis factor-alpha-induced apoptosis was also suppressed in ECRG4-overexpressing Jurkat cells. Immunoprecipitation assay demonstrated that ECRG4 is associated with procaspase-8. The inhibitory mechanism included the inhibition of caspase-8 activity and Bid cleavage. Since ECRG4 expression is downregulated in activated T cells, our results suggest that ECRG4 is a novel antiapoptotic gene which is involved in the negative regulation of caspase-8-mediated apoptosis in T cells.

Journal Article.  6072 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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