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  • 标题:RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: A negative feedback circuit
  • 本地全文:下载
  • 作者:Youming Xie ; Alexander Varshavsky
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2001
  • 卷号:98
  • 期号:6
  • 页码:3056-3061
  • DOI:10.1073/pnas.071022298
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The RPN4 (SON1, UFD5) protein of the yeast Saccharomyces cerevisiae is required for normal levels of intracellular proteolysis. RPN4 is a transcriptional activator of genes encoding proteasomal subunits. Here we show that RPN4 is required for normal levels of these subunits. Further, we demonstrate that RPN4 is extremely short-lived (t1/2 {approx}2 min), that it directly interacts with RPN2, a subunit of the 26S proteasome, and that rpn4{Delta} cells are perturbed in their cell cycle. The degradation signal of RPN4 was mapped to its N-terminal region, outside the transcription-activation domains of RPN4. The ability of RPN4 to augment the synthesis of proteasomal subunits while being metabolically unstable yields a negative feedback circuit in which the same protein up-regulates the proteasome production and is destroyed by the assembled active proteasome.
  • 关键词:proteolysis ; ubiquitin ; N-end rule ; UFD pathway ; cell cycle
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