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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.

Original publication

DOI

10.1038/cdd.2008.59

Type

Journal article

Journal

Cell Death and Differentiation

Publication Date

09/2008

Volume

15

Pages

1385 - 1395

Addresses

Department of Biology, York College, The City University of New York, Jamaica, NY, USA. iarsov@york.cuny.edu

Keywords

Thymus Gland, B-Lymphocytes, T-Lymphocytes, CD4-Positive T-Lymphocytes, Chromosomes, Artificial, Bacterial, Animals, Mice, Transgenic, Mice, Dexamethasone, Proteins, Green Fluorescent Proteins, Glucocorticoids, Fluorescent Dyes, Lymphocyte Activation, Apoptosis, Autophagy, Apoptosis Regulatory Proteins, Beclin-1