Bcl-xL: Difference between revisions
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== Effects == |
== Effects == |
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Similar to Bcl-2, Bcl-xL has been implicated in the survival of cancer cells by inhibiting the function of [[TP53|p53]], a tumor suppressor. In cancerous mouse cells, those which contained Bcl-xL were able to survive while those that only expressed p53 died in a small |
Similar to Bcl-2, Bcl-xL has been implicated in the survival of cancer cells by inhibiting the function of [[TP53|p53]], a tumor suppressor. In cancerous mouse cells, those which contained Bcl-xL were able to survive while those that only expressed p53 died in a small period of time<ref>{{cite journal|last1=AF|first1=Schott|title=Bcl-XL protects cancer cells from p53-mediated apoptosis|journal=Oncogene|date=1995|volume=11|issue=7|pages=1389-1394|pmid=7478561|url=https://www.ncbi.nlm.nih.gov/pubmed/7478561|accessdate=20 November 2016}}</ref>. |
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== Related proteins == |
== Related proteins == |
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Revision as of 23:17, 20 November 2016
 | This article needs additional citations for verification. (November 2016) |
B-cell lymphoma-extra large (Bcl-xL), encoded by the BCL2-like 1 gene, is a transmembrane molecule in the mitochondria. It is a member of the Bcl-2 family of proteins, and acts as an anti-apoptotic protein by preventing the release of mitochondrial contents such as cytochrome c, which leads to caspase activation and ultimately, programmed cell death.[1]
Function
It is a well-established concept in the field of apoptosis that relative amounts of pro- and anti-survival Bcl-2 family of proteins determine whether the cell will undergo cell death; if more Bcl-xL is present, then pores are non-permeable to pro-apoptotic molecules and the cell survives. However, if Bax and Bak become activated, and Bcl-xL is sequestered away by gatekeeper BH3-only factors (e.g. Bim) causing a pore to form, cytochrome c is released leading to initiation of caspase cascade and apoptotic events.[2]
While the exact signaling pathway of Bcl-xL is still not known, it is believed that Bcl-XL differs highly from Bcl-2 in the their mechanism of inducing apoptosis. Bcl-xL is about ten times more functional than Bcl-2 when induced by the chemotherapy drug, Doxorubicin [3] and can specifically bind to cytochrome C residues, preventing apoptosis [4]. It can also prevent the formation of Apaf-1 and Caspase 9 complex by acting directly upon Apaf-1 rather than Capase 9, as shown in nematode homologs[5].
Clinical Significance
Bcl-xL dysfunction in mice can cause ineffective production of red blood cells, sever anemia, hemolysis, and death. This protein has also been shown as a requirement for heme production [6] and in erythroid lineage, Bcl-xL is a major survival factor responsible for an estimated half of the total survival "signal" proerythroblasts must receive in order to survive and become red cells. Bcl-xL promoter contains GATA-1 and Stat5 sites. This protein accumulates throughout the differentiation, ensuring the survival of erythroid progenitors. Because iron metabolism and incorporation into hemoglobin occurs inside the mitochondria, Bcl-xL was suggested to play additional roles in regulating this process in erythrocytes which could lead to a role in polycythemia vera, a disease where there is an overproduction of erythrocytes.[7]
Effects
Similar to Bcl-2, Bcl-xL has been implicated in the survival of cancer cells by inhibiting the function of p53, a tumor suppressor. In cancerous mouse cells, those which contained Bcl-xL were able to survive while those that only expressed p53 died in a small period of time[8].
Related proteins
Other Bcl-2 proteins include Bcl-2, Bcl-w, Bcl-xs, and Mcl-1.
References
- ^ Korsmeyer, Stanley J. (March 1995). "Regulators of Cell Death". Trends in Genetics. 11 (3): 101–105. doi:10.1016/S0168-9525(00)89010-1. Retrieved 5 November 2016.
- ^ Finucane, Deborah M.; et al. (January 22, 1999). "Bax-induced Caspase Activation and Apoptosis via Cytochromec Release from Mitochondria Is Inhibitable by Bcl-xL". The Journal of Biological Chemistry. 274: 2225–2233. doi:10.1074/jbc.274.4.2225.
{{cite journal}}: Explicit use of et al. in:|last2=(help)CS1 maint: unflagged free DOI (link) - ^ Fiebig, Aline A.; et al. (August 23, 2006). "Bcl-XL is qualitatively different from and ten times more effective than Bcl-2 when expressed in a breast cancer cell line". BMC Cancer. 6 (213). doi:10.1186/1471-2407-6-213.
{{cite journal}}: Explicit use of et al. in:|last2=(help)CS1 maint: unflagged free DOI (link) - ^ Bertini, Ivano; et al. (April 18, 2011). "The Anti-Apoptotic Bcl-xL Protein, a New Piece in the Puzzle of Cytochrome C Interactome". PLOS One. doi:10.1371/journal.pone.0018329.
{{cite journal}}: Explicit use of et al. in:|last2=(help)CS1 maint: unflagged free DOI (link) - ^ Hu, Yuanming (February 21, 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proceedings of the National Academy of Sciences in the US. 95 (8): 4386-4391. Retrieved 20 November 2016.
- ^ Rhodes, Melissa M.; et al. (May 17, 2005). "Bcl-xL prevents apoptosis of late-stage erythroblasts but does not mediate the antiapoptotic effect of erythropoietin". Blood Journal. 106 (5). doi:10.1182/blood-2004-11-4344.
{{cite journal}}: Explicit use of et al. in:|last2=(help) - ^ M, Silva; et al. (February 26, 1998). "Expression of Bcl-x in erythroid precursors from patients with polycythemia vera". New England Journal of Medicine. 338 (9): 564–571. doi:10.1056/NEJM199802263380902.
{{cite journal}}: Explicit use of et al. in:|last2=(help) - ^ AF, Schott (1995). "Bcl-XL protects cancer cells from p53-mediated apoptosis". Oncogene. 11 (7): 1389–1394. PMID 7478561. Retrieved 20 November 2016.