Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33ING1 candidate tumor suppressor.
Previous studies suggest that tumor suppressors may play significant roles in blocking the growth of cells during cellular senescence. We therefore studied the potential involvement of a novel growth inhibitor and candidate tumor suppressor gene called ING1, which we have cloned recently (I. Garkavtsev, A. Kazarov, A. Gudkov, and K. Riabowol, Nat. Genet. 14:415-420, 1996), in the process of cellular senescence. Our results show that the RNA and protein levels of ING1 were 8- to 10-fold higher in senescent cells than in young, proliferation-competent human diploid fibroblasts. Expression of the nuclear p33ING1 protein was regulated during the cell cycle, reaching maximal levels during DNA synthesis. Chronic expression of antisense ING1 RNA reproducibly resulted in extension of the proliferative life span of normal human fibroblasts by approximately seven population doublings.
Garkavtsev
I
I
Department of Medical Biochemistry, University of Calgary, Alberta, Canada. igarkavt@acs.ucalgary.ca
Riabowol
K
K
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006131:Growth Inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013489:Suppression, Genetic; D014162:Transfection; D025521:Tumor Suppressor Proteins
D000952:Antigens, Polyomavirus Transforming; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins