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Cytoplasmic retention of p-Erk1/2 and nuclear accumulation of actin proteins during cellular senescence in human diploid fibroblasts.

Authors
Lim, IK; Won Hong, K; Kwak, IH; Yoon, G; Park, SC
Citation
Mechanisms of ageing and development, 119(3):113-130, 2000
Journal Title
Mechanisms of ageing and development
ISSN
0047-63741872-6216
Abstract
In order to investigate the role of signal transduction and the related changes of actin cytoskeleton organization in the process of cellular senescence, H-ras double mutants--V12S35, V12G37 and V12C40--proteins were expressed constitutively in human diploid fibroblast (HDF) cells by retrovirus infection at PD26. Constitutive expression of V12S35, V12G37 and V12C40 proteins induced premature senescence at PD38, PD47 and PD50, respectively, in contrast to the control cells at PD59. Premature senescence was evidenced by the slow cellular growth rate and SA-beta-galactosidase expression accompanied by morphological changes such as flat and large cell shape. Senescent HDF cells as well as the H-ras mutant expressers accumulated p-Erk1/2 in the cytoplasm with increased MEK activity and failed to translocate it to nuclei on EGF stimulation. Senescent HDF cells as well as V12S35 and V12G37 expressers were unable to export actin fibers from nucleus to cytoplasm, form stress fibers through the MAPK and Ral.GDS pathways. Perinuclear expression of Racl was prominent in the HDF cells and V12C40 expresser, while translocation of Racl from perinucleus to nucleus and strong expression of RhoA were observed in the V12S35 expresser. In summary, the induced premature senescence by H-ras double mutants were accompanied by nuclear accumulation of actin and Racl proteins, cytoplasmic retention of p-Erk1/2 and marked induction of RhoA expression mainly through dysregulation of the MEK pathway.
MeSH terms
Actins/*metabolismBiological TransportCell Aging/*physiologyCell Nucleus/metabolismCells, CulturedChildCytoplasm/metabolismDiploidyEnzyme ActivationFibroblasts/cytology/metabolismHumansMaleMitogen-Activated Protein Kinase 1/*metabolismMitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinases/*metabolismMutagenesisProto-Oncogene Proteins p21(ras)/metabolismRetroviridae/physiologyrac1 GTP-Binding Protein/biosynthesisrhoA GTP-Binding Protein/biosynthesis
PMID
11080532
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
임, 인경윤, 계순
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