期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 98, 期 6, 页码 3056-3061出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.071022298
关键词
proteolysis; ubiquitin; N-end rule; UFD pathway; cell cycle
资金
- NIDDK NIH HHS [R56 DK039520, R01 DK039520, R37 DK039520, DK39520] Funding Source: Medline
- NIGMS NIH HHS [R01 GM031530, GM31530] Funding Source: Medline
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 (t(1/2) approximate to 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.
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