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.
Funding
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.
| Funders | Funder number |
|---|---|
| National Institutes of Health (NIH) | |
| National Institute of General Medical Sciences | R01GM064606 |
Keywords
- Bmi-1
- Degradation
- Proteasome
- RING finger
- Ubiquitin
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology