Inactivation of p53 and life span extension of human diploid fibroblasts by mot-2.
Normal human lung fibroblasts were transfected with expression plasmids encoding mot-2, an hsp70 family member that is associated with the immortal phenotype. After the empty vector-transfected controls had become senescent and positive for senescence-associated beta-galactosidase (SA-beta-gal), the mot-2-expressing cells continued to proliferate for an additional 12-18 population doublings and showed a young cell morphology and much lower SA-beta-gal activity. The tumor suppressor p53 was found to be transcriptionally inactivated in life span-extended cells. We have thus shown for the first time that overexpression of mot-2 in normal human cells is able to permit their temporary escape from senescence.
Kaula
S C
SC
National Institute of Bioscience and Human Technology, AIST, Tsukuba, Ibaraki, Japan.
Reddelb
R R
RR
Sugiharac
T
T
Mitsuia
Y
Y
Wadhwac
R
R
D002455:Cell Division; D002460:Cell Line; D048429:Cell Size; D016922:Cellular Senescence; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008168:Lung; D024101:Mitochondrial Proteins; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D024101:Mitochondrial Proteins; D016159:Tumor Suppressor Protein p53; D001616:beta-Galactosidase