The BCL-2 family member BID plays a role during embryonic development in addition to its BH3-only protein function by acting in parallel to BAX, BAK and BOK
- Author(s)
- Ke, FS; Holloway, S; Uren, RT; Wong, AW; Little, MH; Kluck, RM; Voss, AK; Strasser, A;
- Journal Title
- EMBO Journal
- Publication Type
- epub ahead of print
- Abstract
- The intrinsic apoptosis pathway, regulated by the BCL-2 protein family, is essential for embryonic development. Using mice lacking all known apoptosis effectors, BAX, BAK and BOK, we have previously defined the processes during development that require apoptosis. Rare Bok(-/-) Bax(-/-) Bak(-/-) triple knockout (TKO) mice developed to adulthood and several tissues that were thought to require apoptosis during development appeared normal. This raises the question if all apoptosis had been abolished in the TKO mice or if other BCL-2 family members could act as effectors of apoptosis. Here, we investigated the role of BID, generally considered to link the extrinsic and intrinsic apoptosis pathways, acting as a BH3-only protein initiating apoptosis upstream of BAX and BAK. We found that Bok(-/-) Bax(-/-) Bak(-/-) Bid(-/-) quadruple knockout (QKO) mice have additional developmental anomalies compared to TKO mice, consistent with a role of BID, not only upstream but also in parallel to BAX, BAK and BOK. Mitochondrial experiments identified a small cytochrome c-releasing activity of full-length BID. Collectively, these findings suggest a new effector role for BID in the intrinsic apoptosis pathway.
- Publisher
- EMBO Press
- Keywords
- Bak; Bax; Bid; apoptosis; embryonic development
- Research Division(s)
- Blood Cells And Blood Cancer; Epigenetics And Development
- PubMed ID
- 35758142
- Publisher's Version
- https://doi.org/10.15252/embj.2021110300
- NHMRC Grants
- NHMRC/1116937, NHMRC/1081421, NHMRC/1113133,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-07-04 08:56:57
Last Modified: 2022-07-04 09:00:40