Abstract
NF-Y, a heterotrimeric CCAAT binding protein, may have a role in regulating some G1/S genes whose expressions are attenuated during replicative senescence [Matuoka and Chen (1999) Exp Cell Res 253: 365–371]. The hallmark of replicative senescence is the loss of dividing potential. Hence, attenuation of G1/S gene expressions may be causally related to aging. To understand how NF-Y is involved in regulating G1/S genes during replicative senescence, we have examined the expressions of three NF-Y subunit genes in human IMR-90 cells over the entire course of their life-span. The mRNA levels of NF-YA, B, and C did not show any age-dependent change. In contrast, the protein level of NF-YA exhibited a significant and progressive decrease during cell senescence. Cross-linking experiments indicated that NF-Y may interact with proteins such as GCN5 and P/CAF. Co-transfection of cells with plasmid encoding NF-YA protein enhanced the expression of reporter gene fused with G1/S gene promoter that contains NF-Y sites. In contrast, co-transfection with plasmid encoding the dominant negative NF-YA mutant suppressed the expression of the reporter genes. Transient transfection of human cells with dominant negative NF-YA mutant could lead to an increase in neutral β-galactosidase activity, a marker of cell senescence. These results support the view that NF-Y may have a role in cell senescence.
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Matuoka, K., Chen, K.Y. Possible role of subunit A of nuclearfactor Y (NF-YA) in normal human diploidfibroblasts during senescence. Biogerontology 1, 261–271 (2000). https://doi.org/10.1023/A:1010094431748
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DOI: https://doi.org/10.1023/A:1010094431748