A novel candidate tumor suppressor, ING1, is involved in the regulation of apoptosis.
We have recently cloned a novel growth inhibitor and candidate tumor suppressor called p33ING1 (I. Garkavtsev et al., Nature Genet., 14: 415-420, 1996). Because some tumor suppressors participate in the regulation of apoptosis, we hypothesized that the ING1 gene may also play a role in this process. Our results show that p33ING1 levels increase upon the induction of apoptosis in P19 teratocarcinoma cells by serum deprivation. Elevated expression of ING1 in P19 and rodent fibroblast cells containing a tetracycline-controlled human c-myc gene enhanced the extent of serum starvation-induced apoptosis. This suggests that the pathway by which ING1 modulates cell death is synergistic with Myc-dependent apoptosis. Conversely, constitutive expression of an antisense construct of INGI conferred protection against apoptosis in these cells. These data support the idea that loss of proper ING1 function may facilitate tumorigenesis, in part, by reducing the cell's sensitivity to apoptosis.
Helbing
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CC
Department of Medical Biochemistry, The University of Calgary, Alberta, Canada.
Veillette
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C
Riabowol
K
K
Johnston
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RN
Garkavtsev
I
I
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018797:Cell Cycle Proteins; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C501503:ING1 protein, human; C501505:Ing1 protein, mouse; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D025521:Tumor Suppressor Proteins