Cleavage of Calnexin Caused by Apoptotic Stimuli: Implication for the Regulation of Apoptosis

Authors: Takenori Takizawa¹; Chizuru Tatematsu¹; Kimi Watanabe¹; Kanefusa Kato¹; Yoshinobu Nakanishi²

Source: The Journal of Biochemistry, Volume 136, Number 3, September 2004 , pp. 399-405(7)

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Abstract:

Calnexin is an endoplasmic reticulum (ER)-resident molecular chaperone that plays an essential role in the correct folding of membrane proteins. We found that calnexin is subjected to partial cleavage in apoptotic mouse cells. Both ER stress–inducing and ER stress–non-inducing apoptotic stimuli caused the cleavage of calnexin, indicating that this event does not always occur downstream of ER stress. The inhibition of caspases that target the amino acid sequence DXXD abrogated calnexin cleavage in apoptotic stimulus-treated cells. In addition, disruption of one of two DXXD sequences located in the cytoplasmic domain caused calnexin to escape cleavage during apoptosis. Furthermore, calnexin was cleaved in vitro by recombinant caspase-3 or caspase-7. Finally, the overexpression of a presumed cleavage product of calnexin partly inhibited apoptosis. These results collectively suggest that caspase-3 or caspase-7 cleaves calnexin, whose cleaved product leads to the attenuation of apoptosis.

Document Type: Research article

DOI: http://dx.doi.org/10.1093/jb/mvh133

Affiliations: 1: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai 480-0392; and 2: Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0934

Publication date: 2004-09-01