2007年7月
Diphtheria toxin mutant CRM197 possesses weak EF2-ADP-ribosyl activity that potentiates its anti-tumorigenic activity
JOURNAL OF BIOCHEMISTRY
- ,
- ,
- ,
- ,
- ,
- 巻
- 142
- 号
- 1
- 開始ページ
- 95
- 終了ページ
- 104
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1093/jb/mvm116
- 出版者・発行元
- OXFORD UNIV PRESS
CRM197, a mutated diphtheria toxin (DT), has long been recognized to be a non-toxic protein. Based on its non-toxic feature, this protein has been utilized for various purposes, including as an inhibitor of heparin-binding EGF-like growth factor (HB-EGF) and as an immunological adjuvant for vaccination. Here we show evidence that CRM197 has a weak toxicity. This toxicity was observed in cells over-expressing the DT receptor/proHB-EGF, but not in parental cells, indicating that the toxicity was mediated through DT receptor. CRM197 did not show any toxicity toward DT-resistant cells, which have a mutation in elongation factor 2, and a cell-free assay revealed the existence of weak EF-2-ADP ribosylation activity in fragment A of CRM197. Thus, the present study indicates a requirement for specific care in the use of CRM197 at a high dosage, although the toxicity of CRM197 is about 106 times less than that of wild-type DT. We found that a monoclonal antibody to DT inhibited CRM197 toxicity, but did not affect the inhibitory activity of CRM197 toward HB-EGF-induced mitogenic activity. CRM197 strongly inhibits tumour growth in nude mice. The anti-DT monoclonal antibody administered with CRM197 reduced the anti- tumourigenic effect of CRM197, indicating that the toxicity of CRM197 potentiates its anti-tumourigenic effect.
- リンク情報
-
- DOI
- https://doi.org/10.1093/jb/mvm116
- CiNii Articles
- http://ci.nii.ac.jp/naid/10020098014
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/17525101
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000251645800013&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1093/jb/mvm116
- ISSN : 0021-924X
- CiNii Articles ID : 10020098014
- PubMed ID : 17525101
- Web of Science ID : WOS:000251645800013