Phosphorylation of telomeric repeat binding factor 1 (TRF1) by Akt causes telomere shortening.
Telomeric repeat binding factor 1 (TRF1) belongs to the shelterin complex, which modulates the telomere structures. Akt/protein kinase B activation caused genomic instability and contributes to tumorigenesis, although the molecular mechanism remained little known. Here, we show the direct interaction between Akt and TRF1. In vitro kinase assays showed the phosphorylation of a putative Akt phosphorylation site (Threonine 273) in wild type TRF1, but not the mutant TRF1 (T273A), by Akt. Overexpression of Akt decreased telomere length in a HTC cell line. These results indicate that Akt plays an important role in telomere length regulation, contributing to genomic instability and tumorigenesis.
Chen
Yen-Chung
YC
Institutes of Biochemistry & Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Teng
Shu-Chun
SC
Wu
Kou-Juey
KJ
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D042822:Genomic Instability; D006801:Humans; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D016297:Mutagenesis, Site-Directed; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000502:physiology*; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D027361:Organic Anion Transporters; D051057:Proto-Oncogene Proteins c-akt; D035321:Telomeric Repeat Binding Protein 1; C487009:SLCO6A1 protein, human