Bushan Xie1, Lin Zhao, Hao Chen, Bo Jin, Zebin Mao, Zhi Yao. 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.
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.
Authors: Tapan K Maity; Abhilash Venugopalan; Ilona Linnoila; Constance M Cultraro; Andreas Giannakou; Roxanne Nemati; Xu Zhang; Joshua D Webster; Daniel Ritt; Sarani Ghosal; Heinz Hoschuetzky; R Mark Simpson; Romi Biswas; Katerina Politi; Deborah K Morrison; Harold E Varmus; Udayan Guha Journal: Cancer Discov Date: 2015-03-03 Impact factor: 39.397
Authors: Tim Schomann; Kimia Mirzakhani; Julia Kallenbach; Jing Lu; Seyed Mohammad Mahdi Rasa; Francesco Neri; Aria Baniahmad Journal: Biomolecules Date: 2022-07-29