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MCL-1–dependent leukemia cells are more sensitive to chemotherapy than BCL-2–dependent counterparts
| Content Provider | Scilit |
|---|---|
| Author | Brunelle, Joslyn K. Ryan, Jeremy Yecies, Derek Opferman, Joseph T. Letai, Anthony |
| Copyright Year | 2009 |
| Description | Myeloid cell leukemia sequence 1 (MCL-1) and B cell leukemia/lymphoma 2 (BCL-2) are anti-apoptotic proteins in the BCL-2 protein family often expressed in cancer. To compare the function of MCL-1 and BCL-2 in maintaining cancer survival, we constructed complementary mouse leukemia models based on Eμ-Myc expression in which either BCL-2 or MCL-1 are required for leukemia maintenance. We show that the principal anti-apoptotic mechanism of both BCL-2 and MCL-1 in these leukemias is to sequester pro-death BH3-only proteins rather than BAX and BAK. We find that the MCL-1–dependent leukemias are more sensitive to a wide range of chemotherapeutic agents acting by disparate mechanisms. In common across these varied treatments is that MCL-1 protein levels rapidly decrease in a proteosome-dependent fashion, whereas those of BCL-2 are stable. We demonstrate for the first time that two anti-apoptotic proteins can enable tumorigenesis equally well, but nonetheless differ in their influence on chemosensitivity. |
| Related Links | http://jcb.rupress.org/content/187/3/429.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779245/pdf |
| Ending Page | 442 |
| Page Count | 14 |
| Starting Page | 429 |
| DOI | 10.1083/jcb.200904049 |
| Journal | Journal of Cell Biology |
| Issue Number | 3 |
| Volume Number | 187 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2009-10-26 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Survival Function Leukemia Mcl Bcl Anti Apoptotic Proteins Journal: Journal of Cell Biology (Vol- 187, Issue- 3) |
| Content Type | Text |
