Regulating the genome surveillance system: miRNAs and the p53 super family.
The p53 gene super family consists of three members; TP53, TP63 and TP73, encoding proteins p53, p63 and p73. Whilst p63 appears to have an essential role in embryonic development with a less clear role in carcinogenesis, irregularities in p53 and p73 signalling are implicated in tumour formation. As such, p53 is a tumour suppressor which is mutated in over 50% cancers and p73 was recently formally classified as a tumour suppressor based on data showing p73 deficient mice generate spontaneous tumours similar to those observed in p53 null mice. Dysregulation of both p53 and p73 has been correlated with cancer progression in many cell types and although mutation of these genes is often observed, some form of p53/p73 deregulation likely occurs in all tumour cells. The discovery that complementary micro RNAs (miRNAs) are able to target both of these genes provides a potential new means of perturbing p53/p73 signalling networks in cancer cells. Here we summarise the current literature regarding the involvement of miRNAs in the modulation of p53 family proteins and cancer development and detail the use of in silico methods to reveal key miRNA targets.
Bailey
Sarah G
SG
School of Medicine, University of Southampton, Southampton, SO16 6YD, UK.
Sanchez-Elsner
Tilman
T
Stephanou
Anastasis
A
Cragg
Mark S
MS
Townsend
Paul A
PA
D017398:Alternative Splicing; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016678:Genome; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D009369:Neoplasms / Q000276:immunology / Q000503:physiopathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins