Oncogenic transformation by beta-catenin: deletion analysis and characterization of selected target genes.
Genetic analysis of beta-catenin-induced oncogenic transformation in chicken embryo fibroblasts (CEF) revealed the following prerequisites for oncogenicity: (1) removal of the N terminal phosphorylation sites targeted by glycogen synthase kinase 3beta (GSK3beta), (2) retention of the N terminal transactivation domain, and (3) retention of the armadillo repeats. The C terminal transactivation domain played an ancillary role in the transformation of CEF. There was a rough correlation between the transforming activity of various beta-catenin constructs and their transactivation of the TOPFLASH reporter. Expression levels of the candidate target genes of beta-catenin-LEF, cyclin D1 and myc were not correlated with each other or with the transforming activity of beta-catenin constructs. A new target gene, coding for inositol hexakisphosphate kinase 2 (IP6K2) was identified. Its expression showed concordance with the transforming activity of beta-catenin constructs.
Aoki
Masahiro
M
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, CA 92037, USA. maoki@scripps.edu
Sobek
Vera
V
Maslyar
Daniel J
DJ
Hecht
Andreas
A
Vogt
Peter K
PK
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002642:Chick Embryo; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D016259:Genes, myc; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D051176:beta Catenin
D056741:Cyclin D; D016213:Cyclins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3