BCL-2: the pendulum of the cell fate.
The homeostasis of normal tissues is a balance between cell proliferation and cell death. Alterations of both pathways contribute to a clonal expansion of cancer cells. Bcl-2 and its family play an important role in the regulation of the apoptotic pathway. Apoptosis or programmed cell death is an active form of cell suicide that is characterized by specific morphological and biochemical events. These include cleavege of genomic DNA into oligonucleosome-length DNA fragments by endonucleases, chromatin condensation and marginalization, nuclear fragmentation, plasma membrane blebbing, and cell shrinkage. Though the role of apoptosis is clearly defined in the maintaining of physiological tissue homeostasis, several pathological conditions and external factors cause apoptosis. Anticancer drugs and radiation, two of the most important tools in the cancer treatment, cause apoptotic cell death. The understanding of the mechanisms underlying the regulation of the apoptosis in response to different types of DNA damage might provide relevant information to improve cancer treatment. In this review we mainly discuss bcl-2 and its partners in human cancers and how their disregulation might contribute to the development and the difficult treatment of cancer.
Blandino
G
G
Dept. of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. liblan@dapsas1.weizmann.ac.il
Strano
S
S
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2 / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000628:therapy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein
C494819:BAD protein, human; C494772:BAK1 protein, human; C091732:BCL2-associated athanogene 1 protein; C096816:BCL2-related protein A1; C494820:Bad protein, mouse; C494773:Bak1 protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051818:Replication Protein C