Journal
CELL DEATH AND DIFFERENTIATION
Volume 15, Issue 9, Pages 1385-1395Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2008.59
Keywords
beclin 1; autophagy; T cell; B cell; apoptosis
Categories
Funding
- The National Institutes of Health MBRS SCORE [S06GM08153-31]
- NINDS [R21RNS055683, R01RNS060123]
- NIH NIAID [HHSN2662000500021C]
- Department of Neurology
- Minority Access to Biomedical Research (MARC)
- National Institutes of Health [T32GM8498-11]
- [U19 AI06231]
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Beclin 1/Atg6 is an essential component of the evolutionary conserved PtdIns(3)-kinase (Vps34) protein complex that regulates macroautophagy (autophagy) in eukaryotic cells and also interacts with antiapoptotic Bcl-2 family members, Bcl-2, and Bcl-x(L). To elucidate the physiological function of Beclin 1, we generated transgenic mice producing a green fluorescent Beclin 1 protein (Beclin 1-GFP) under Beclin 1 endogenous regulation. The beclin 1-GFP transgene is functional because it completely rescues early embryonic lethality in beclin 1-deficient mice. The transgenic mice appear normal, with undetected change in basal autophagy levels in different tissues, despite the additional expression of functional Beclin 1-GFP. Staining of Beclin 1-GFP shows mostly diffuse cytoplasmic distribution in various tissues. Detailed analysis of the transgene expression by flow cytometry reveals a Bcl-2-like biphasic expression pattern in developing T and B cells, as well as differential regulation of expression in mature versus immature thymocytes following in vitro stimulation. Moreover, thymocytes expressing high Beclin 1-GFP levels appear increasingly sensitive to glucocorticoid-induced apoptosis in vitro. Our results, therefore, support a role for Beclin 1 in lymphocyte development involving cross talk between autophagy and apoptosis.
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