title: HOXA5-twist interaction alters p53 homeostasis in breast cancer cells.
abstract: The homeotic gene HOXA5 has been shown to play an important role in breast tumorigenesis. We have shown that loss of p53 correlated with loss of a developmentally regulated transcription factor, HOXA5, in primary breast cancer. Searching for potential protein interacting partners we found that HOXA5 binds to an anti-apoptotic protein, Twist. Furthermore, Twist-overexpressing MCF-7 cells displayed a deregulated p53 response to gamma-radiation and decreased regulation of downstream target genes. Using a p53-promoter-reporter system, we demonstrated that HOXA5 could partially restore the inhibitory effects of Twist on p53 target genes. These effects are likely mediated through both the transcriptional up-regulation of p53 and the protein-protein interaction between HOXA5 and Twist. Thus, the loss of HOXA5 expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis.
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Stasinopoulos
authors.forename: Yelena
authors.initials: Y
authors.lastname: Mironchik
authors.forename: Ana
authors.initials: A
authors.lastname: Raman
authors.forename: Flonne
authors.initials: F
authors.lastname: Wildes
authors.forename: Paul
authors.initials: P
authors.lastname: Winnard
authors.forename: Venu
authors.initials: V
authors.lastname: Raman
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005720:Gamma Rays; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1; D020798:Two-Hybrid System Techniques
chemical_list: C489213:HOXA5 protein, human; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1