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Annu Rev Immunol. 1995;13:513-43.

Regulation of lymphocyte survival by the bcl-2 gene family.

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Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.


The control of cell survival is of central importance in tissues with high cell turnover such as the lymphoid system, and its disruption may be a critical step in tumorigenesis. Genes homologous to bcl-2, the oncogene implicated in human follicular lymphoma, play a key role in regulating physiologic cell death (apoptosis). Bcl-2 and its relatives bcl-x and bax encode intracellular membrane-bound proteins that share homology in three domains with a wider family of viral and cellular proteins. The Bcl-2 and Bcl-x proteins enhance the survival of lymphocytes and other cell types but do not promote their proliferation. High levels of Bax or of a smaller Bcl-x variant antagonize the survival function of Bcl-2. The mechanism by which Bcl-2 promotes cell survival remains unknown, but it appears to require association with Bax. Bcl-2 may combat the action of cysteine proteases thought to trigger apoptosis. Bcl-2 is not essential for embryogenesis or lymphoid development. However, upregulation of Bcl-2 appears to be the normal mechanism for positive selection of developing lymphocytes, and its continued expression is critical for survival of mature peripheral B and T cells. Constitutive expression of Bcl-2 does not abrogate deletion of self-reactive lymphocytes, nor disturb T lymphoid homeostasis; however, it substantially increases the pool of mature noncycling B cells. The risk of B lymphoid tumors is also enhanced, probably because Bcl-2 can countermand the apoptotic action of other oncoproteins such as Myc. Expression in tumors of bcl-2 and other cell survival genes may constitute a major barrier to the success of genotoxic cancer therapy.

[Indexed for MEDLINE]

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