Downregulation of transcription factor, Sp1, during cellular senescence.
We found that the protein level of Sp1 transcription factor decreases as normal human fibroblasts undergo replicative aging. Sp1 also undergoes a rapid decrease in the protein level and activity in MCF-7 cells that are induced to a state of cellular senescence. In the cells treated with other DNA damaging chemicals such as actinomycin D and H(2)O(2), the Sp1 level decreased progressively as well. Inhibition of ATM/ATR kinases prevented this downregulation, suggesting that DNA damage signaling is involved in the regulation of the Sp1. This decrease in Sp1 protein level is due to the accelerated proteasomal degradation since a proteasome inhibitor, ALLN, blocked this downregulation. Therefore, the global decrease in gene transcription frequently reported in aging cells and tissues could be attributed at least in part to the decrease in Sp1 level.
Oh
Ji-Eun
JE
Department of Life Science, University of Seoul, Dongdaemungu, Jeonnongdong 90, Seoul 130-743, Republic of Korea.
Han
Jung-A
JA
Hwang
Eun Seong
ES
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D004249:DNA Damage / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016329:Sp1 Transcription Factor; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases