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The mitogen‐inducible gene‐6 is involved in regulation of cellular senescence in normal diploid fibroblasts
Author(s) -
Xie Bushan,
Zhao Lin,
Chen Hao,
Jin Bo,
Mao Zebin,
Yao Zhi
Publication year - 2013
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1111/boc.201200052
Subject(s) - senescence , biology , microbiology and biotechnology , gene knockdown , kinase , protein kinase a , gene expression , suppressor , gene , genetics
Background information 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.