Antagonism between MCL-1 and PUMA governs stem/progenitor cell survival during hematopoietic recovery from stress
- Author(s)
- Delbridge, AR; Opferman, JT; Grabow, S; Strasser, A;
- Journal Title
- Blood
- Publication Type
- Journal Article
- Abstract
- Understanding the critical factors that govern recovery of the hematopoietic system from stress, such as during anti-cancer therapy and bone marrow transplantation, is of clinical significance. We investigated the importance of the pro-survival proteins MCL-1 and BCL-XL in stem/progenitor cell survival and fitness during hematopoietic recovery from stress. Loss of a single Mcl-1 allele, which reduced MCL-1 protein levels, severely compromised hematopoietic recovery from myelo-ablative challenge and following bone marrow transplantation, while BCL-XL was dispensable in both contexts. We identified inhibition of pro-apoptotic PUMA as the key role of MCL-1 in both settings, with Mcl-1+/-;Puma-/- mice completely protected from the deleterious effects of loss of one Mcl-1 allele. These results reveal the molecular mechanisms that govern cell survival during hematopoietic recovery from stress.
- Research Division(s)
- Molecular Genetics Of Cancer
- PubMed ID
- 25847014
- Publisher's Version
- https://doi.org/10.1182/blood-2015-01-621250
- NHMRC Grants
- NHMRC/1016701, NHMRC/1020363,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-04-28 11:00:05
Last Modified: 2016-04-20 12:08:46