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Translocational inefficiency of intracellular proteins in senescence of human diploid fibroblasts.

Lim, IK; Hong, KW; Kwak, IH; Yoon, G; Park, SC
Annals of the New York Academy of Sciences, 928176-181, 2001
Journal Title
Annals of the New York Academy of Sciences
In order to investigate signal transduction pathways and related changes of actin cytoskeleton organization in cellular senescence, H-ras double mutants--V12S35, V12G37, and V12C40--were constitutively expressed in human foreskin fibroblast (HDF). 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, V12S35 and V12G37 expressers, revealed a failure to export actin fiber from nucleus to cytoplasm and also to form stress fibers. Perinuclear expression of Rac1 was prominent in the HDF cells and V12C40 expresser; however, in the V12S35 expresser, translocation of Rac1 from perinucleus to nucleus and strong expression of RhoA were obvious. In summary, the H-ras double mutant expressers induced premature senescence through the MEK pathway, accompanied by nuclear accumulation of actin and Rac1 proteins, cytoplasmic retention of p-Erk1/2, and marked induction of RhoA expression, suggesting the translocational inefficiency of the intracellular proteins in the senescent HDF cells.
MeSH terms
3T3 Cells/drug effects3T3 Cells/ultrastructureActins/metabolismActive Transport, Cell Nucleus*AnimalsBlood Proteins/metabolismCell Aging/physiology*Cell Nucleus/metabolismCell Surface ExtensionsCyclin-Dependent Kinase Inhibitor p16/physiologyCytoplasm/metabolismCytoskeletal Proteins/metabolismCytoskeleton/physiology*Cytoskeleton/ultrastructureDiploidyFibroblasts/cytology*Fibroblasts/metabolismGenes, p16Genes, p53Genes, ras*HumansMAP Kinase Kinase Kinase 1*MAP Kinase Signaling System*MaleMembrane Proteins/metabolismMiceMicrofilament Proteins/metabolismMitogen-Activated Protein Kinase 1/metabolismMitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinases/metabolismPhosphoproteins/metabolismProtein Isoforms/metabolismProtein-Serine-Threonine Kinases/metabolismProto-Oncogene Proteins p21(ras)/physiologyStress Fibers/metabolismTumor Suppressor Protein p53/physiologyrac1 GTP-Binding Protein/metabolismrhoA GTP-Binding Protein/metabolism
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Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
임, 인경윤, 계순
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