BH3‐only proteins: Integrated control point of apoptosis

• Published in: International Journal of Cancer Vol. 119; no. 9; pp. 2036 - 2043
• Main Authors: Shibue, Tsukasa, Taniguchi, Tadatsugu
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley 01.11.2006; Wiley Subscription Services, Inc., A Wiley Company; Wiley-Liss
• Subjects: Apoptosis; Apoptosis Regulatory Proteins; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; bcl-2 Homologous Antagonist-Killer Protein; bcl-2 Homologous Antagonist-Killer Protein - genetics; bcl-2 Homologous Antagonist-Killer Protein - metabolism; bcl-2-Associated X Protein; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Bcl‐2 family; BH3‐only proteins; Biological and medical sciences; Humans; Medical sciences; mitochondria; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Protein Processing, Post-Translational; Proto-Oncogene Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Stress, Physiological; Transcription, Genetic; Tumor Suppressor Protein p53; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Human; BH3-only proteins; Review; Malignant tumor; Bcl-2 family; Mitochondria; Cancerology; TP53 Gene; Cell death; Analog; C-Onc gene; Genetics; Control point; Protooncogene; Apoptosis; Tumor suppressor gene; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21751

Bcl‐2 family proteins play central roles in the regulation of most, if not all, apoptotic pathways, and hence this family plays a critical role in oncogenesis. The Bcl‐2 homology 3 (BH3)‐only members of this family are “proapoptotic,” promoting apoptosis by sensing cellular stresses: that is, they are activated or induced in response to stress stimuli. These BH3‐only proteins then interfere with the function of “prosurvival” Bcl‐2 family members, thereby promoting the progression of apoptosis. It has long been recognized that the induction and activation of each of the BH3‐only proteins are subject to the type of stress stimulus. Although it was originally assumed that all the BH3‐only proteins exert similar effects on the downstream apoptotic machinery, recent studies have uncovered their distinct functional properties, indicating the operation of more intricate, versatile control mechanisms of apoptosis. In this review, we will summarize recent findings on the diversity in the activation and function of BH3‐only proteins. In particular, we focus on the overlapping and individual roles of 2 BH3‐only proteins, Puma and Noxa, in the context of the apoptotic response induced by the tumor suppressor p53. © 2006 Wiley‐Liss, Inc.