Inhibitors of proteasome induced premature senescence in normal human fibroblasts. Besides morphological alteration and expression of senescence marker genes, these cells manifested senescence-associated heterochromatic foci under staining of the nuclei with DAPI similar to normally senescent cells. These results suggest that declining ability in protein degradation may be involved in the formation of heterochromatic foci in senescent fibroblasts.

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-To elucidate the role of ribosomes in the manifestation of adriamycin toxicity, ribos--otic model. This revealed that adriamycin toxicity was enhanced by loss of the Egd1 or Egd2 subunits of mitochondria or endoplasmic reticulum and in transcriptional activation in the nucleus. Because the loss of the Btt1 subunit had no effect on adriamycin sensitivity, the NAC conformation responsible for resistance to adriamycin appears to be the Egd1/Egd2 complex. We propose that functional NAC in the ribosome is involved in resistance to adriamycin toxicity.

No abstract