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Cell Signal. 2014 Sep;26(9):1870-7. doi: 10.1016/j.cellsig.2014.05.003. Epub 2014 May 9.

Mig-6 participates in the regulation of cell senescence and retinoblastoma protein phosphorylation.

Author information

1
Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: malgorzata.milewska@ucd.ie.
2
Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland; School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: walter.kolch@ucd.ie.

Abstract

Mitogen-inducible gene-6 (Mig-6) is a cytosolic multiadaptor protein that is best known for its role as a negative feedback regulator of epidermal growth factor receptor (EGFR) mediated signalling. Alternative roles of Mig-6 are becoming increasingly recognised. Consistently with this, Mig-6 was demonstrated to be involved in a broad spectrum of cellular events including tumour suppression which may include the induction of cellular senescence. Here, we investigated the mechanisms of Mig-6 induced premature cell senescence. Endogenous Mig-6 is poorly expressed in young fibroblasts, whilst its expression rises in cells presenting with typical features of senescence. Overexpression of Mig-6 is sufficient to trigger premature cellular senescence of early passage diploid lung fibroblasts (WI-38). Interestingly, Mig-6 overexpression reduced retinoblastoma protein (pRb) phosphorylation at the inactivating Ser249/Thr252 sites. We also found that phosphorylation of these sites in pRb is increased in the presence of the B-Raf V600E oncogenic mutation. We further show that Mig-6 overexpression reduces B-Raf V600E mediated pRb inactivation and preserves pRb function.

KEYWORDS:

B-Raf V600E; Cellular senescence; Human diploid lung fibroblasts; Mig-6; Phospho-retinoblastoma (Ser249/Thr252)

PMID:
24815188
DOI:
10.1016/j.cellsig.2014.05.003
[Indexed for MEDLINE]

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