Abstract
Bmi-1 is a polycomb protein that plays an important role in tumor cell development and maintaining stem cell populations of many cell lineages. Here we identify a polymorphism in human Bmi-1 that changes a cysteine within its RING domain to tyrosine. This C18Y polymorphism is associated with a significant decrease in Bmi-1 level and its elevated ubiquitination, suggesting that it is being destroyed by the ubiquitin-proteasome system. Consistent with this, treating cells with the proteasome inhibitor MG-132 significantly increases C18Y Bmi-1 levels. This is the first example of a polymorphism in Bmi-1 that reduces levels of this important protein. Structured summary: MINT-6948574: Bmi-1 (uniprotkb:P35226) physically interacts (MI:0218) with Ubiquitin (uniprotkb:P62988) by anti tag coimmunoprecipitation (MI:0007).
| Original language | English |
|---|---|
| Pages (from-to) | 960-964 |
| Number of pages | 5 |
| Journal | FEBS Letters |
| Volume | 583 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 18 2009 |
Bibliographical note
Funding Information:We would like to thank Dr. Dan Noonan for providing MG-132, Dr. Haining Zhu for the anti-ubiquitin antibody and HEK293 cells, and to other members of the laboratory for insightful discussions. This work was supported by NIH Grant GM64606 to K.D.S.
Keywords
- Bmi-1
- Degradation
- Proteasome
- RING finger
- Ubiquitin
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology