دورية أكاديمية
Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding site
| العنوان: | Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding site |
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| المؤلفون: | Warr, Matthew R., Mills, John R., Nguyen, Mai, Lemaire-Ewing, Stephanie, Baardsnes, Jason, Sun, Karen L. W., Malina, Abba, Young, Jason C., Jeyaraju, anny V., O'Connor-McCourt, Maureen, Pellegrini, Luca, Pelletier, Jerry, Shore, Gordon C. |
| بيانات النشر: | American Society for Biochemistry and Molecular Biology |
| سنة النشر: | 2011 |
| المجموعة: | National Research Council Canada: NRC Publications Archive |
| الوصف: | Mcl-1, a pro-survival member of the Bcl-2 family located at the mitochondrial outer membrane, is subject to constitutive ubiquitylation by the Bcl-2 homology 3-only E3 ligase, Mule/ Lasu1, resulting in rapid steady-state degradation via the proteasome. Insertion of newly synthesized Mcl-1 into the mitochondrial outer membrane is dependent on its C-terminal transmembrane segment, but once inserted, the N terminus of a portion of the Mcl-1 molecules can be subject to proteolytic processing. Remarkably, this processing requires an intact electrochemical potential across the inner membrane. Three lines of evidence directed at the endogenous protein, however, indicate that the resulting Mcl-1ΔN isoform resides in the outer membrane: (i) full-length Mcl-1 and Mcl-1ΔN resist extraction by alkali but are accessible to exogenous protease; (ii) almost the entire populations of Mcl-1 and Mcl-1ΔN are accessible to the membrane-impermeant Cys-reactive agent 4-acetamido-4'- [(iodoacetyl)amino]stilbene-2,2'-disulfonic acid; and (iii) Mcl-1 and Mcl-1ΔN exhibit equivalent chemical cross-linking to Bak in intact mitochondria, an Mcl-1 binding partner located in the outer membrane. In addition to the Mule Bcl-2 homology 3 domain, we show that interaction between Mcl-1 and Mule also requires the extreme N terminus of Mcl-1, which is lacking in Mcl-1ΔN. Thus, Mcl-1ΔN does not interact with Mule, exhibits reduced steady-state ubiquitylation, evades the hyper-rapid steady-state degradation that is observed for full-length Mcl-1 in response to treatments that limit global protein synthesis, and confers resistance to UV stress-induced cell death ; Peer reviewed: Yes ; NRC publication: Yes |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| تدمد: | 0021-9258 1083-351X |
| العلاقة: | The Journal of Biological Chemistry, Volume: 286, Issue: 28, Publication date: 2011-07-15, Pages: 25098–25107 |
| DOI: | 10.1074/jbc.M111.218321 |
| الإتاحة: | https://doi.org/10.1074/jbc.M111.218321Test https://nrc-publications.canada.ca/eng/view/accepted/?id=8b5f7b01-6802-4f8a-b1f1-82ab9030e83eTest https://nrc-publications.canada.ca/eng/view/object/?id=8b5f7b01-6802-4f8a-b1f1-82ab9030e83eTest https://nrc-publications.canada.ca/fra/voir/objet/?id=8b5f7b01-6802-4f8a-b1f1-82ab9030e83eTest |
| رقم الانضمام: | edsbas.EAF2D23F |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00219258 1083351X |
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| DOI: | 10.1074/jbc.M111.218321 |