Regulating p73 isoforms in human tumours.
Although mutations in the TP73 gene are extremely rare in human tumours, altered expression is common. In some tumours, most notably leukaemias and lymphomas, expression of TP73 is reduced, suggesting a tumour suppressor role. In contrast, TP73 is over-expressed in many other tumour types, implying that it has oncogenic functions in human tumourigenesis. These conflicting scenarios can be reconciled by the observations that the TP73 gene produces p53-like isoforms (TAp73) and anti-p53 isoforms (DeltaTAp73). Thus, loss of TAp73 or over-expression of DeltaTAp73 should each promote oncogenic transformation, and the balance of expression of the opposing isoforms is the crucial factor. The mechanisms that regulate expression of TP73 isoforms are therefore of great interest. Recent data provide evidence for interacting roles of ZEB1, p300, and a polymorphic 73 bp deletion in intron 1 of the human TP73 gene in this process. Importantly, alterations to the proposed regulatory pathway for controlling TP73 isoform expression in colorectal cancer are associated with adverse clinico-pathological characteristics. Because p73 is also associated with tumour chemosensitivity, these new findings should provide prognostic information and have the potential to guide future therapeutic decisions.
Coates
P J
PJ
Pathology and Neurosciences, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK. p.j.coates@dundee.ac.uk
D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000071799:Zinc Finger E-box-Binding Homeobox 1
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1