REGULATION OF LYMPHOCYTE SURVIVAL BY THE BCL-2 GENE FAMILY

Cory, S

Author(s): Cory, S;
Journal Title: ANNUAL REVIEW OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: 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.
Publisher: ANNUAL REVIEWS INC
Keywords: PROGRAMMED CELL-DEATH; WILD-TYPE P53; HUMAN FOLLICULAR LYMPHOMA; MYELOID LEUKEMIC-CELLS; C-MYC; TRANSGENIC MICE; B-CELLS; T-CELLS; THYMOCYTE APOPTOSIS; PROTOONCOGENE BCL-2
Publisher's Version: https://doi.org/10.1146/annurev.immunol.13.1.513
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Creation Date: 1995-01-01 12:00:00