title: Akt promotes tumorigenesis in part through modulating genomic instability via phosphorylating XLF.
abstract: To maintain genome stability, mammalian cells have developed a delicate, yet efficient, system to sense and repair damaged DNA, including two evolutionarily conserved DNA damage repair (DDR) pathways: homologous recombination (HR) and non-homologous-end-joining (NHEJ). Deregulation in these repair pathways may lead to genomic instability and subsequent human diseases, including cancer. On the other hand, hyper-activation of the oncogenic Akt signaling pathway has been observed in almost all solid tumors. Emerging evidence has begun to reveal a possible role of active Akt in regulating DDR, possibly through suppression of HR. However, whether and how Akt regulates NHEJ remains largely undefined. To this end, we recently reported that Akt impairs NHEJ by phosphorylating XLF at T181, to trigger its dissociation from the functional DNA ligase IV (LIG4)/XRCC4 complex. Here, we provide an additional perspective discussing how Akt is activated upon DNA damage to regulate DNA repair pathways as well as the cellular apoptotic responses.
authors.affiliation: a Department of Pathology ; Beth Israel Deaconess Medical Center ; Harvard Medical School ; Boston , MA USA.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Gan
authors.forename: Pengda
authors.initials: P
authors.lastname: Liu
authors.forename: Wenyi
authors.initials: W
authors.lastname: Wei
mesh_terms: D000595:Amino Acid Sequence; D063646:Carcinogenesis / Q000235:genetics*; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D042822:Genomic Instability; D059765:Homologous Recombination; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C000607893:LIG4 protein, human; C508551:NHEJ1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D011088:DNA Ligases; D045643:DNA Repair Enzymes; D000072481:DNA Ligase ATP
keywords: Akt; DNA repair; HR; NHEJ; Oncogene; XLF; cell cycle; cell signaling; phophorylation; signaling; tumorigenesis