title: Functional association between Wwox tumor suppressor protein and p73, a p53 homolog.
abstract: The WWOX gene is a recently cloned tumor suppressor gene that spans the FRA16D fragile region. Wwox protein contains two WW domains that are generally known to mediate protein-protein interaction. Here we show that Wwox physically interacts via its first WW domain with the p53 homolog, p73. The tyrosine kinase, Src, phosphorylates Wwox at tyrosine 33 in the first WW domain and enhances its binding to p73. Our results further demonstrate that Wwox expression triggers redistribution of nuclear p73 to the cytoplasm and, hence, suppresses its transcriptional activity. In addition, we show that cytoplasmic p73 contributes to the proapoptotic activity of Wwox. Our findings reveal a functional cross-talk between p73 and Wwox tumor suppressor protein.
authors.affiliation: Kimmel Cancer Institute, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
authors.forename: Rami I
authors.initials: RI
authors.lastname: Aqeilan
authors.forename: Yuri
authors.initials: Y
authors.lastname: Pekarsky
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Herrero
authors.forename: Alexey
authors.initials: A
authors.lastname: Palamarchuk
authors.forename: Jean
authors.initials: J
authors.lastname: Letofsky
authors.forename: Teresa
authors.initials: T
authors.lastname: Druck
authors.forename: Francesco
authors.initials: F
authors.lastname: Trapasso
authors.forename: Shuang-Yin
authors.initials: SY
authors.lastname: Han
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.forename: Kay
authors.initials: K
authors.lastname: Huebner
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins