Bcl-2-regulated apoptosis: mechanism and therapeutic potential

Author(s): Adams, JM; Cory, S;
Details: Publication Year 2007-10,Volume 19,Issue #5,Page 488-496
Journal Title: CURRENT OPINION IN IMMUNOLOGY
Publication Type: Journal Article
Abstract: Apoptosis is essential for tissue homeostasis, particularly in the hematopoietic compartment, where its impairment can elicit neoplastic or autoimmune diseases. Whether stressed cells live or die is largely determined by interplay between opposing members of the Bcl-2 protein family. Bcl-2 and its closest homologs promote cell survival, but two other factions promote apoptosis. The BH3-only proteins sense and relay stress signals, but commitment to apoptosis requires Bax or Bak. The BH3-only proteins appear to activate Bax and Bak indirectly, by engaging and neutralizing their pro-survival relatives, which otherwise constrain Bax and Bak from permeabilizing mitochondria. The Bcl-2 family may also regulate autophagy and mitochondrial fission/fusion. Its pro-survival members are attractive therapeutic targets in cancer and perhaps autoimmunity and viral infections.
Publisher: CURRENT BIOLOGY LTD
Keywords: BCL-X-L; DNA-DAMAGE RESPONSE; PROGRAMMED CELL-DEATH; BH3 MIMETIC ABT-737; BH3-ONLY PROTEINS; FAMILY-MEMBERS; PROSURVIVAL BCL-2; PROAPOPTOTIC BAX; MITOCHONDRIAL FRAGMENTATION; ENDOPLASMIC-RETICULUM
Publisher's Version: https://doi.org/10.1016/j.coi.2007.05.004
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-10-01 12:00:00