Autophagy as a cell death and tumor suppressor mechanism.
Autophagy is characterized by sequestration of bulk cytoplasm and organelles in double or multimembrane autophagic vesicles, and their delivery to and subsequent degradation by the cell's own lysosomal system. Autophagy has multiple physiological functions in multicellular organisms, including protein degradation and organelle turnover. Genes and proteins that constitute the basic machinery of the autophagic process were first identified in the yeast system and some of their mammalian orthologues have been characterized as well. Increasing lines of evidence indicate that these molecular mechanisms may be recruited by an alternative, caspase-independent form of programmed cell death, named autophagic type II cell death. In some settings, autophagy and apoptosis seem to be interconnected positively or negatively, introducing the concept of 'molecular switches' between them. Additionally, mitochondria may be central organelles integrating the two types of cell death. Malignant transformation is frequently associated with suppression of autophagy. The recent implication of tumor suppressors like Beclin 1, DAP-kinase and PTEN in autophagic pathways indicates a causative role for autophagy deficiencies in cancer formation. Autophagic cell death induction by some anticancer agents underlines the potential utility of its induction as a new cancer treatment modality.
Gozuacik
Devrim
D
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Kimchi
Adi
A
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D064550:Death-Associated Protein Kinases; D015852:Eukaryotic Initiation Factor-2 / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D009857:Oncogenes; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D015852:Eukaryotic Initiation Factor-2; D018840:HSP70 Heat-Shock Proteins; C490979:HSPA4L protein, human; D006360:Heat-Shock Proteins; D025801:Ubiquitin; D019869:Phosphatidylinositol 3-Kinases; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins