Acetylation of the cell-fate factor dachshund determines p53 binding and signaling modules in breast cancer. Oncotarget 2013 Jun;4(6):923-35
Date
06/27/2013Pubmed ID
23798621Pubmed Central ID
PMC3757249DOI
10.18632/oncotarget.1094Scopus ID
2-s2.0-84880830761 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
Breast cancer is a leading form of cancer in the world. The Drosophila Dac gene was cloned as an inhibitor of the hyperactive epidermal growth factor (EGFR), ellipse. Herein, endogenous DACH1 co-localized with p53 in a nuclear, extranucleolar compartment and bound to p53 in human breast cancer cell lines, p53 and DACH1 bound common genes in Chip-Seq. Full inhibition of breast cancer contact-independent growth by DACH1 required p53. The p53 breast cancer mutants R248Q and R273H, evaded DACH1 binding. DACH1 phosphorylation at serine residue (S439) inhibited p53 binding and phosphorylation at p53 amino-terminal sites (S15, S20) enhanced DACH1 binding. DACH1 binding to p53 was inhibited by NAD-dependent deacetylation via DACH1 K628. DACH1 repressed p21CIP1 and induced RAD51, an association found in basal breast cancer. DACH1 inhibits breast cancer cellular growth in an NAD and p53-dependent manner through direct protein-protein association.
Author List
Chen K, Wu K, Gormley M, Ertel A, Wang J, Zhang W, Zhou J, Disante G, Li Z, Rui H, Quong AA, McMahon SB, Deng H, Lisanti MP, Wang C, Pestell RGMESH terms used to index this publication - Major topics in bold
AcetylationAmino Acid Sequence
Apoptosis
Binding Sites
Breast Neoplasms
Cell Cycle Checkpoints
Cell Differentiation
Cell Line, Tumor
Chromatin
DNA Damage
Eye Proteins
Female
Gene Expression
HEK293 Cells
Humans
Mutation
Promoter Regions, Genetic
Protein Binding
Sequence Homology, Amino Acid
Signal Transduction
Transcription Factors
Transfection
Tumor Suppressor Protein p53
