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Cited by 310

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Nix and Nip3 Form a Subfamily of Pro-apoptotic Mitochondrial Proteins

Open access
Chen, Gao, Cizeau, Jeannick, Vande Velde, Christine, Park, Jae Hoon, Bozek, Gracjan, Bolton, James, Shi, Lianfa, Dubik, Don, Greenberg, Arnold·1999·Journal of Biological Chemistry

Abstract

We have identified Nix, a homolog of the E1B 19K/Bcl-2 binding and pro-apoptotic protein Nip3. Human and murine Nix have a 56 and 53% amino acid identity to human and murine Nip3, respectively. The carboxyl terminus of Nix, including a transmembrane domain, is highly homologous to Nip3 but it bears a longer and distinct asparagine/proline-rich N terminus. Human Nip3 maps to chromosome 14q11.2-q12, whereas Nix/BNip3L was found on 8q21. Nix encodes a 23. 8-kDa protein but it is expressed as a 48-kDa protein, suggesting that it homodimerizes similarly to Nip3. Following transfection, Nix protein undergoes progressive proteolysis to an 11-kDa C-terminal fragment, which is blocked by the proteasome inhibitor lactacystin. Nix colocalizes with the mitochondrial matrix protein HSP60, and removal of the putative transmembrane domain (TM) results in general cytoplasmic and nuclear expression. When transiently expressed, Nix and Nip3 but not TM deletion mutants rapidly activate apoptosis. Nix can overcome the suppressers Bcl-2 and Bcl-XL, although high levels of Bcl-XL expression will inhibit apoptosis. We propose that Nix and Nip3 form a new subfamily of pro-apoptotic mitochondrial proteins.

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Metadata

Authors
Chen, G., Cizeau, J., Vande Velde, C., Park, J. H., Bozek, G., Bolton, J., Shi, L., Dubik, D., & Greenberg, A.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1999-01
Volume
274
Issue
1
Pages
7-10
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2005528779
Cited by
310
References
1
FWCI
4.13
Type
journal article
Language
en
Open access
hybrid

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