![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
![[thumbnail of 9680oa.pdf]](https://edoc.mdc-berlin.de/style/images/fileicons/application_pdf.png) |
PDF
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
5MB |
| Item Type: | Article |
|---|---|
| Title: | Mcl-1 determines the Bax dependency of Nbk/Bik-induced apoptosis |
| Creators Name: | Gillissen, B., Essmann, F., Hemmati, P.G., Richter, A., Richter, A., Oztop, I., Chinnadurai, G., Doerken, B. and Daniel, P.T. |
| Abstract: | B cell lymphoma 2 (Bcl-2) homology domain 3 (BH3)-only proteins of the Bcl-2 family are important functional adaptors that link cell death signals to the activation of Bax and/or Bak. The BH3-only protein Nbk/Bik induces cell death via an entirely Bax-dependent/Bak-independent mechanism. In contrast, cell death induced by the short splice variant of Bcl-x depends on Bak but not Bax. This indicates that Bak is functional but fails to become activated by Nbk. Here, we show that binding of myeloid cell leukemia 1 (Mcl-1) to Bak persists after Nbk expression and inhibits Nbk-induced apoptosis in Bax-deficient cells. In contrast, the BH3-only protein Puma disrupts Mcl-1-Bak interaction and triggers cell death via both Bax and Bak. Targeted knockdown of Mcl-1 overcomes inhibition of Bak and allows for Bak activation by Nbk. Thus, Nbk is held in check by Mcl-1 that interferes with activation of Bak. The finding that different BH3-only proteins rely specifically on Bax, Bak, or both has important implications for the design of anticancer drugs targeting Bcl-2. |
| Keywords: | Adenoviridae, Apoptosis, Apoptosis Regulatory Proteins, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Benzimidazoles, Biological Models, Carbocyanines, Cell Line, Cell Membrane Permeability, Cytochromes C, Fluorescent Dyes, HCT116 Cells, Kidney, Membrane Proteins, Mitochondria, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins, Prostatic Neoplasms, Proto-Oncogene Proteins c-bcl-2, Transgenes, Tumor Cell Line |
| Source: | Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Volume: | 179 |
| Number: | 4 |
| Page Range: | 701-715 |
| Date: | 19 November 2007 |
| Official Publication: | https://doi.org/10.1083/jcb.200703040 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
