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Biol Cell. 2013 Oct;105(10):488-99. doi: 10.1111/boc.201200052. Epub 2013 Jul 24.

The mitogen-inducible gene-6 is involved in regulation of cellular senescence in normal diploid fibroblasts.

Author information

1
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.

Abstract

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.

KEYWORDS:

Cellular senescence; FOXO3a; Human fibroblasts; Mig-6

PMID:
23746120
DOI:
10.1111/boc.201200052
[Indexed for MEDLINE]

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