期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 27, 页码 11209-11214出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0700816104
关键词
degradation; rescue of function
资金
- NIBIB NIH HHS [R01 EB001991, EB001991] Funding Source: Medline
- NIGMS NIH HHS [P20 GM072015, GM072015] Funding Source: Medline
Controlling protein function through posttranslational manipulations has emerged as an attractive complementary technology to existing genetic systems. Often these methods involve developing pharmacological agents to probe protein function without the need to generate a unique compound for each protein family. One common strategy uses small molecules that act as chemical inducers of dimerization by mediating the interaction of two proteins. Herein we report the use of a chemical inducer of dimerization for the development of a posttranslational technology for the manipulation of protein function. This system, split ubiquitin for the rescue of function (SURF), places the complementation of genetically split ubiquitin under the control of rapamycin-induced dimerization of FK506-binding protein and FKBP12-rapamycin-binding protein. Before complementation a degron dooms a protein of interest for destruction by the proteasorne. Addition of rapamycin results in a proteolytic shunt away from degradation by inducing ubiquitin complementation and deavage of the protein of interest from the degron. importantly, the native protein is rescued. We characterized this system with firefly luciferase and went on to apply it to members of three important dasses of proteins: proteases (caspase-3), kinases (v-Src), and transcription factors (Smad3). This general strategy should allow for inducible rescue of a variety of proteins in such a way that their native structure and function are maintained.
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