The do's and don'ts of p53 isoforms
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Reiner U. Jänicke
Abstract
Upon DNA damage and other stresses, the transcription factor p53 elicits numerous responses including DNA repair, cell cycle arrest and apoptosis, properties that make p53 the prototype tumor suppressor. In addition, p53 also transactivates genes whose products act in an anti-apoptotic manner providing strong evidence that p53 exhibits both tumor suppressive and tumorigenic functions. Although several events were postulated to contribute to the p53-mediated decision process, the precise mechanism(s) that governs p53 activities is still elusive. Recently, it was found that the p53 gene allows expression of at least nine different isoforms that arise from multiple splicing events and the usage of alternative promoters. Several of these isoforms were shown to critically interfere with the function of the full-length p53 mainly by acting in a dominant-negative manner. However, an isoform-dependent selective activation of p53 target genes was also observed. Furthermore, certain p53 isoforms are aberrantly expressed in various tumors strongly implying their involvement in tumorigenic events. Thus, p53 isoforms may represent crucial determinants in p53-mediated decision processes whose precise functions (their do's and don'ts) are only beginning to emerge.
©2009 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
- Guest Editorial
- Highlight: ‘Regenerative Hepatology’
- Highlight: Regenerative Hepatology
- The do's and don'ts of p53 isoforms
- Mechanisms of liver disease: cross-talk between the NF-κB and JNK pathways
- Immunologic hurdles of therapeutic stem cell transplantation
- Ancestral vascular tube formation and its adoption by tumors
- Cellular plasticity of the pancreas
- Hepatic and pancreatic stellate cells in focus
- Interplay between host cell and hepatitis C virus in regulating viral replication
- Epidermal growth factor receptor signaling in liver cell proliferation and apoptosis
- The chemokine scavenging receptor D6 limits acute toxic liver injury in vivo
- Hepatic differentiation of pluripotent stem cells
- Protein Structure and Function
- Effect of curcumin on amyloidogenic property of molten globule-like intermediate state of 2,5-diketo-d-gluconate reductase A
- Cell Biology and Signaling
- Specific induction of migration and invasion of pancreatic carcinoma cells by RhoC, which differs from RhoA in its localisation and activity
- Autoregulatory control of the p53 response by Siah-1L-mediated HIPK2 degradation
Artikel in diesem Heft
- Guest Editorial
- Highlight: ‘Regenerative Hepatology’
- Highlight: Regenerative Hepatology
- The do's and don'ts of p53 isoforms
- Mechanisms of liver disease: cross-talk between the NF-κB and JNK pathways
- Immunologic hurdles of therapeutic stem cell transplantation
- Ancestral vascular tube formation and its adoption by tumors
- Cellular plasticity of the pancreas
- Hepatic and pancreatic stellate cells in focus
- Interplay between host cell and hepatitis C virus in regulating viral replication
- Epidermal growth factor receptor signaling in liver cell proliferation and apoptosis
- The chemokine scavenging receptor D6 limits acute toxic liver injury in vivo
- Hepatic differentiation of pluripotent stem cells
- Protein Structure and Function
- Effect of curcumin on amyloidogenic property of molten globule-like intermediate state of 2,5-diketo-d-gluconate reductase A
- Cell Biology and Signaling
- Specific induction of migration and invasion of pancreatic carcinoma cells by RhoC, which differs from RhoA in its localisation and activity
- Autoregulatory control of the p53 response by Siah-1L-mediated HIPK2 degradation
