bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria - PubMed (original) (raw)
bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria
M González-García et al. Development. 1994 Oct.
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-x beta, that results from an unspliced bcl-x transcript. bcl-x beta 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.
Similar articles
- Cloning and molecular characterization of mouse bcl-x in B and T lymphocytes.
Fang W, Rivard JJ, Mueller DL, Behrens TW. Fang W, et al. J Immunol. 1994 Nov 15;153(10):4388-98. J Immunol. 1994. PMID: 7963517 - bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death.
Boise LH, González-García M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nuñez G, Thompson CB. Boise LH, et al. Cell. 1993 Aug 27;74(4):597-608. doi: 10.1016/0092-8674(93)90508-n. Cell. 1993. PMID: 8358789 - Functional and biological analysis of Bcl-xL expression in human osteosarcoma.
Wang ZX, Yang JS, Pan X, Wang JR, Li J, Yin YM, De W. Wang ZX, et al. Bone. 2010 Aug;47(2):445-54. doi: 10.1016/j.bone.2010.05.027. Epub 2010 May 23. Bone. 2010. PMID: 20580954 - Importance of the Bcl-2 family in cell death regulation.
McDonnell TJ, Beham A, Sarkiss M, Andersen MM, Lo P. McDonnell TJ, et al. Experientia. 1996 Oct 31;52(10-11):1008-17. doi: 10.1007/BF01920110. Experientia. 1996. PMID: 8917732 Review. - BCL-X and the apoptotic machinery of lymphoma cells.
Xerri L, Hassoun J, Devilard E, Birnbaum D, Birg F. Xerri L, et al. Leuk Lymphoma. 1998 Feb;28(5-6):451-8. doi: 10.3109/10428199809058352. Leuk Lymphoma. 1998. PMID: 9613974 Review.
Cited by
- Synthesis, bioactivity assessment, molecular docking and ADMET studies of new chromone congeners exhibiting potent anticancer activity.
Abo-Salem HM, El Souda SSM, Shafey HI, Zoheir KMA, Ahmed KM, Mahmoud K, Mahrous KF, Fawzy NM. Abo-Salem HM, et al. Sci Rep. 2024 Apr 26;14(1):9636. doi: 10.1038/s41598-024-59606-2. Sci Rep. 2024. PMID: 38671055 Free PMC article. - Protection from cisplatin-induced hearing loss with lentiviral vector-mediated ectopic expression of the anti-apoptotic protein BCL-XL.
Nassauer L, Staecker H, Huang P, Renslo B, Goblet M, Harre J, Warnecke A, Schott JW, Morgan M, Galla M, Schambach A. Nassauer L, et al. Mol Ther Nucleic Acids. 2024 Feb 19;35(1):102157. doi: 10.1016/j.omtn.2024.102157. eCollection 2024 Mar 12. Mol Ther Nucleic Acids. 2024. PMID: 38450280 Free PMC article. - Bcl2l1 Deficiency in Osteoblasts Reduces the Trabecular Bone Due to Enhanced Osteoclastogenesis Likely through Osteoblast Apoptosis.
Moriishi T, Kawai Y, Fukuyama R, Matsuo Y, He YW, Akiyama H, Asahina I, Komori T. Moriishi T, et al. Int J Mol Sci. 2023 Dec 10;24(24):17319. doi: 10.3390/ijms242417319. Int J Mol Sci. 2023. PMID: 38139148 Free PMC article. - Truncated Dyrk1A aggravates neuronal apoptosis by inhibiting ASF-mediated Bcl-x exon 2b inclusion.
Zhang S, Zhong J, Xu L, Wu Y, Xu J, Shi J, Gu Z, Li X, Jin N. Zhang S, et al. CNS Neurosci Ther. 2024 Apr;30(4):e14493. doi: 10.1111/cns.14493. Epub 2023 Oct 21. CNS Neurosci Ther. 2024. PMID: 37864462 Free PMC article. - Computational design of BclxL inhibitors that target transmembrane domain interactions.
Duart G, Elazar A, Weinstein JY, Gadea-Salom L, Ortiz-Mateu J, Fleishman SJ, Mingarro I, Martinez-Gil L. Duart G, et al. Proc Natl Acad Sci U S A. 2023 Mar 14;120(11):e2219648120. doi: 10.1073/pnas.2219648120. Epub 2023 Mar 7. Proc Natl Acad Sci U S A. 2023. PMID: 36881618 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials