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Mechanisms of Bcl-2 protein function
H-.G. Wang and J.C. Reed
The Burnham Institute, Program on Apoptosis & Cell
Death Research, La Jolla, CA, USA
Offprint requests to: Dr. Hong-Gang
Wang, The Burnham Institute, Program on Apoptosis & Cell Death Research,
1091 N. Torrey Pines Rd, La Jolla, CA 92037, USA
Summary. The Bcl-2 protein
blocks a distal step in an evolutionarily conserved pathway for programmed
cell death and apoptosis. The gene encoding this protein was first discovered
because of its involvement in the t(14;18) chromosomal translocations commonly
found in B-cell lymphomas. Overexpression of Bcl-2 also occurs in many other
types of human cancers, and prevents cell death induced by nearly all anticancer
drugs and radiation. Since the discovery of Bcl-2 over ten years ago, several
cellular and viral homologs have been identified, some of which suppress
cell death and others which promote apoptosis. Many of these proteins can
interact with each other through a complex network of homo- and heterodimers.
Though functionally important, dimerization events still do not explain
in a broader sense how these proteins actually control cell life and death.
Recent findings that Bcl-2 can function both as an ion channel and as an
adapter or docking protein however are beginning to provide insights into
the molecular mechanisms through which these proteins regulate the programmed
cell death pathway in normalcy and disease. Histol Histopathol 13, 521-530
Key words: Bcl-2, Raf-1, Apoptosis
DOI: 10.14670/HH-13.521
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