Abstract
ABSTRACT Most examples of cell death in animals are controlled by a genetic program that is activated within the dying cell. The apoptotic process is further regulated by a set of genes that act as repressors of cell death. Of these, bcl-2 is expressed in a variety of embryonic and postnatal tissues which suggests a critical role for bcl-2 in organogenesis and tissue homeostasis. Surprisingly, mutant mice with targeted disruption of bcl-2 appear normal at birth and complete maturation of lymphoid tissues before succumbing to fulminant lymphopenia and polycystic renal disease by 2-5 weeks of age. This suggests that there may be genes other than bcl-2 that can regulate apoptosis during development. To begin to investigate this possibility, we have cloned and characterized the murine bcl-x gene, whose human counterpart displays striking homology to bcl-2. The predicted murine bcl-xL gene product exhibits a high level of amino acid identity (97%) to its human counterpart. Just like Bcl-2, the murine bcl-xL gene product can act as a dominant inhibitor of cell death upon growth factor withdrawal. In addition, the bulk of the bcl-xL product localizes to the periphery of mitochondria as assessed by a bcl-xL-tag expression system, suggesting that both Bcl-2 and Bcl-xL proteins prevent cell death by a similar mechanism. bcl-xL is the most abundant bcl-x mRNA species expressed in embryonic and adult tissues. The levels of bcl-xL mRNA appear higher than those of bcl-2 during embryonal development and in several adult organs including bone marrow, brain, kidney and thymus. In addition to bcl-xL, we have identified another form of bcl-x mRNA, bcl-xβ, that results from an unspliced bcl-x transcript. bcl-xβ mRNA is expressed in various embryonic and postnatal tissues. Surprisingly, the expression of bcl-xS (a negative regulator of programmed cell death) was undetectable by a sensitive S1-nuclease assay and polymerase chain reaction analysis of mouse tissues. Based on its tissue and developmental patterns of expression, it appears that bcl-x may play an important role in the regulation of cell death during development and tissue homeostasis.
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Dates
Type | When |
---|---|
Created | 4 years, 4 months ago (April 25, 2021, 9:33 p.m.) |
Deposited | 8 months, 2 weeks ago (Dec. 17, 2024, 6:47 p.m.) |
Indexed | 51 minutes ago (Sept. 2, 2025, 9:54 p.m.) |
Issued | 30 years, 11 months ago (Oct. 1, 1994) |
Published | 30 years, 11 months ago (Oct. 1, 1994) |
Published Online | 30 years, 11 months ago (Oct. 1, 1994) |
Published Print | 30 years, 11 months ago (Oct. 1, 1994) |
@article{Gonz_lez_Garc_a_1994, title={bcl-xLx is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria}, volume={120}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.120.10.3033}, DOI={10.1242/dev.120.10.3033}, number={10}, journal={Development}, publisher={The Company of Biologists}, author={González-García, Maribel and Pérez-Ballestero, Rafael and Ding, Liyun and Duan, Linda and Boise, Lawrence H. and Thompson, Craig B. and Núñez, Gabriel}, year={1994}, month=oct, pages={3033–3042} }