Acetylation of the cell-fate factor dachshund determines p53 binding and signaling modules in breast cancer.
Acetylation of the cell-fate factor dachshund determines p53 binding and signaling modules in breast cancer.
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DOI：
10.18632/oncotarget.1094
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发表时间：
2013-06
期刊：
影响因子：
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通讯作者：
Pestell RG
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文献类型：
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作者：
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 RG
乳腺癌是世界上最常见的癌症之一。果蝇Dac基因被克隆为过度活跃的表皮生长因子（EGFR）的抑制剂，椭圆形。本文中，内源性DACH 1与p53共定位于细胞核、核仁间室中，并与人乳腺癌细胞系中的p53结合，p53和DACH 1结合Chip-Seq中的共同基因。DACH 1完全抑制乳腺癌非接触性生长需要p53。p53乳腺癌突变体R248 Q和R273 H逃避DACH 1结合。丝氨酸残基（S439）的DACH 1磷酸化抑制p53结合，而p53氨基端位点（S15、S20）的磷酸化增强DACH 1结合。DACH 1与p53的结合被NAD依赖性的脱乙酰化通过DACH 1 K628抑制。DACH 1抑制p21 CIP 1并诱导RAD 51，这是在基底乳腺癌中发现的一种关联。DACH 1通过直接的蛋白质-蛋白质结合以NAD和p53依赖性方式抑制乳腺癌细胞生长。
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.