Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt.

Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt. Research Abstract Details 

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Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt. Abstract Text:

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 proteasome. Addition of rapamycin results in a proteolytic shunt away from degradation by inducing ubiquitin complementation and cleavage 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 classes 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.

Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt. Publishing Authors By Initials

For similar proteins: ubiquitins: ubiquitin research abstracts see: proteins: ubiquitins: ubiquitin research

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Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 11209-14

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 11

MONTH: 06

YEAR: 2007

Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt. Keywords Mesh Terms:

KEYWORDS: Ubiquitin

MESH TERMS: physiology

Chemical & Substance for Abstract: Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt. Information

Substance Name: Peptide Hydrolases

Registry Number: EC 3.4.-

Grant and Affiliation Information for Small-molecule-mediated rescue of protein function by an inducible proteolytic shunt.

AFFILIATION: Laboratory of Synthetic Protein Chemistry, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM072015

ACRONYM: GM

MEDLINETA: Proc Natl Acad Sci U S A

REFSOURCE: Proc Natl Acad Sci U S A. 2007 Jul 10;10

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