p73, a sophisticated p53 family member in the cancer world.
p73 belongs to a family of p53-related nuclear transcription factors that includes p53, p73 and p63. The overall structure and sequence homology indicates that a p63/p73-like protogene is the ancestral gene, whereas p53 evolved later in higher organisms. In accordance with their structural similarity, p73 functions in a manner analogous to p53 by inducing tumor cell apoptosis and participating in the cell cycle checkpoint control through transactivating an overlapping set of p53/p73-target genes. In sharp contrast to p53, however, p73 is expressed as two NH(2)-terminally distinct isoforms including transcriptionally active (TA) and transcriptionally inactive (DeltaN) forms. DeltaNp73, which has oncogenic potential, acts in a dominant negative manner against TAp73 as well as p53. p73 is induced to be stabilized in response to a subset of DNA-damaging agents in a way that is distinct from that of p53, and exerts its pro-apoptotic activity. Several lines of evidence suggest that p73 can induce tumor cell apoptosis in a p53-dependent and p53-independent manner. Some tumors exhibit resistance to the p53-dependent apoptotic program, therefore p73, which can induce apoptotic cell death by p53-independent mechanisms, is particularly useful. In this review, we discuss the regulatory mechanisms of p73 activity, and also the functional significance of p73 in the regulation of cellular processes including tumorigenesis, apoptosis and neurogenesis.
Ozaki
Toshinori
T
Division of Biochemistry, Chiba Cancer Center Research Institute, Chuoh-ku, Japan.
Nakagawara
Akira
A
D017398:Alternative Splicing; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009857:Oncogenes; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human