title: The mitogen-inducible gene-6 is involved in regulation of cellular senescence in normal diploid fibroblasts.
abstract: BACKGROUND
  The mitogen-inducible gene-6 (Mig-6) is a non-kinase scaffolding adaptor protein. It has been shown that Mig-6 may play important roles in regulating stress response, maintaining homeostasis and functioning as a tumour suppressor. In this study, we investigated the role of Mig-6 in cellular senescence.
  
  
  RESULTS
  Our results showed that Mig-6 is up-regulated during the senescence process. Functional analysis indicated that cells over-expressing Mig-6 have reduced DNA synthesis and showed the signs of senescence. Knockdown of Mig-6 delayed the initiation of Ras-induced cellular senescence. These results suggest that the increase of Mig-6 expression contributes to establishment of cellular senescence. Furthermore, our results showed that Mig-6 induction of senescence is related to its inhibition of EGF receptor (EGFR)/Erb B signalling. Subsequent analysis of the mechanism responsible for the up-regulation of its expression showed that FOXO3A transcriptionally up-regulates Mig-6 expression via directly binding to the FOXO response element in Mig-6 5'-flanking regulatory sequences.
  
  
  CONCLUSIONS
  Mig-6 induces premature senescence via functioning in regulation of cellular senescence in normal diploid fibroblasts.
authors.affiliation: The Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, Beijing, 100191, China; The Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
authors.forename: Bushan
authors.initials: B
authors.lastname: Xie
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.forename: Zebin
authors.initials: Z
authors.lastname: Mao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016922:Cellular Senescence; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D020218:Response Elements / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C484017:ERRFI1 protein, human; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: Cellular senescence; FOXO3a; Human fibroblasts; Mig-6