title: TAp73β-mediated suppression of cell migration requires p57Kip2 control of actin cytoskeleton dynamics.
abstract: The TP73 gene, a member of the p53 family, due to the use of different promoters and alternative splicing, is transcribed into different isoforms with contrasting attributes and which contribute to its functional diversity. Considerable efforts are made to identify the functional diversity of the p73 splicing variants during tumorigenesis. TAp73α and TAp73β isoforms have been shown to differentially regulate cell cycle progression, differentiation and apoptosis. Interestingly, a particular increase in expression of the TAp73 isoform, in favor of the α splicing variant, has been reported in multiple tumour types. Here, we report a distinctive role for TAp73β isoform in the control of cell migration and invasion. In fact, TAp73β- dependent induction of p57(Kip2) expression accounted for inhibitory effects on the actin cytoskeleton dynamics and thereby cancer cell motility. In contrast, TAp73α is not able to induce p57(Kip2) expression, and exhibits a positive effect on actin cytoskeleton dynamics as well as cell migration and invasion. In conclusion, the inhibitory effect on cell migration and invasion of TAp73β would qualify this distinct p73 isoform as tumor suppressor gene. In contrast, the promoting effect of TAp73α on cell motility and invasion strengthens the potential oncogenic activities of this p73 isoform.
authors.affiliation: Department of Oncology-Pathology, Cancer Centrum Karolinska, Karolinska Institutet, 171 76 Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Rodhe
authors.forename: Edel
authors.initials: E
authors.lastname: Kavanagh
authors.forename: Bertrand
authors.initials: B
authors.lastname: Joseph
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020033:Protein Isoforms; D015533:Transcriptional Activation; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D050761:Cyclin-Dependent Kinase Inhibitor p57; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins