| First Author | Hockings C | Year | 2018 |
| Journal | Cell Death Differ | Volume | 25 |
| Issue | 4 | Pages | 719-732 |
| PubMed ID | 29459767 | Mgi Jnum | J:274137 |
| Mgi Id | MGI:6287193 | Doi | 10.1038/s41418-017-0010-6 |
| Citation | Hockings C, et al. (2018) Mcl-1 and Bcl-xL sequestration of Bak confers differential resistance to BH3-only proteins. Cell Death Differ 25(4):719-732 |
| abstractText | The prosurvival Bcl-2 family proteins Mcl-1 and Bcl-xL inhibit apoptosis by sequestering BH3-only proteins such as Bid and Bim (MODE 1) or the effector proteins Bak and Bax (MODE 2). To better understand the contributions of MODE 1 and MODE 2 in blocking cell death, and thus how to bypass resistance to cell death, we examined prescribed mixtures of Bcl-2 family proteins. In a Bim and Bak mixture, Bcl-xL and Mcl-1 each sequestered not only Bim but also Bak as it became activated by Bim. In contrast, in a Bid and Bak mixture, Bcl-xL preferentially sequestered Bid while Mcl-1 preferentially sequestered Bak. Notably, Bcl-xL could sequester Bak in response to the BH3 mimetic ABT-737, despite this molecule targeting Bcl-xL. These findings highlight the importance of Bak sequestration in resistance to anti-cancer treatments, including BH3 mimetics. |
