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Biochem Biophys Res Commun. 2015 Jan 16;456(3):810-4. doi: 10.1016/j.bbrc.2014.12.024. Epub 2014 Dec 13.

Activation of apoptosis by caspase-3-dependent specific RelB cleavage in anticancer agent-treated cancer cells: involvement of positive feedback mechanism.

Author information

1
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
2
Department of Molecular Target Medicine, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute 480-1195, Japan. Electronic address: umezawa@aichi-med-u.ac.jp.

Abstract

DTCM-glutarimide (DTCM-G) is a newly found anti-inflammatory agent. In the course of experiments with lymphoma cells, we found that DTCM-G induced specific RelB cleavage. Anticancer agent vinblastine also induced the specific RelB cleavage in human fibrosarcoma HT1080 cells. The site-directed mutagenesis analysis revealed that the Asp205 site in RelB was specifically cleaved possibly by caspase-3 in vinblastine-treated HT1080 cells. Moreover, the cells stably overexpressing RelB Asp205Ala were resistant to vinblastine-induced apoptosis. Thus, the specific Asp205 cleavage of RelB by caspase-3 would be involved in the apoptosis induction by anticancer agents, which would provide the positive feedback mechanism.

KEYWORDS:

Apoptosis; Caspase-3; DTCM-glutarimide; RelB; Vinblastine

PMID:
25511695
DOI:
10.1016/j.bbrc.2014.12.024
[Indexed for MEDLINE]

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