ArticleProceedings of the National Academy of Sciences of the United States of America2003
Exploring the functional complexity of cellular proteins by protein knockout.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 54 citations in OpenAlex.
- Programmable protein degraders enable selective knockdown of pathogenic β-catenin subpopulations in vitro and in vivo.Science advances · 2026Article
- An NLP-based method to mine gene and function relationships from published articles.Scientific reports · 2025Article
- Targeted protein degradation using chimeric human E2 ubiquitin-conjugating enzymes.Communications biology · 2024Article
- bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA).Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Broad-Spectrum Proteome Editing with an Engineered Bacterial Ubiquitin Ligase Mimic.ACS central science · 2019Article
- The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Design and Functional Characterization of Synthetic E3 Ubiquitin Ligases for Targeted Protein Depletion.Current protocols in chemical biology · 2018Article
- A recombinant chimeric protein specifically induces mutant KRAS degradation and potently inhibits pancreatic tumor growth.Oncotarget · 2016Article
- Methods: A small-molecule SMASh hit.Nature chemical biology · 2015Article
- Microporation is an efficient method for siRNA-induced knockdown of PEX5 in HepG2 cells: evaluation of the transfection efficiency, the PEX5 mRNA and protein levels and induction of peroxisomal deficiency.Histochemistry and cell biology · 2014Article
- Ubiquibodies, synthetic E3 ubiquitin ligases endowed with unnatural substrate specificity for targeted protein silencing.The Journal of biological chemistry · 2014Article
- Small-molecule control of intracellular protein levels through modulation of the ubiquitin proteasome system.Angewandte Chemie (International ed. in English) · 2014Review
- Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases.Oncogene · 2014Article
- The maternal to zygotic transition in mammals.Molecular aspects of medicine · 2013Review
- The F-box protein FBXO25 promotes the proteasome-dependent degradation of ELK-1 protein.The Journal of biological chemistry · 2013Article
- Engineering new protein-protein interactions on the β-propeller fold by yeast cell surface display.Chembiochem : a European journal of chemical biology · 2013Article
- Fluorescent fusion protein knockout mediated by anti-GFP nanobody.Nature structural & molecular biology · 2011Article
- Maximizing target protein ablation by integration of RNAi and protein knockout.Cell research · 2011Article
- Cullins and cancer.Genes & cancer · 2010Article
- An auxin-based degron system for the rapid depletion of proteins in nonplant cells.Nature methods · 2009Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Comprehensive dissection of protein functions entails more complicated manipulations than simply eliminating the protein of interest. Established knockdown technologies, such as RNA interference, antisense oligodeoxynucleotides, or ribozymes, are limited for specific applications such as modulating protein levels or specific targeting of a posttranslationally modified subpopulation. Here we show that the engineered Skp1, Cullin 1, and F-box-containing betaTrCP substrate receptor ubiquitin-proteolytic system, designated protein knockout, could achieve not only total elimination but also rapid and systematic reduction of a given cellular protein. Stable expression of a single engineered betaTrCP demonstrated simultaneous and sustained degradation of the entire retinoblastoma family proteins. Furthermore, the engineered betaTrCP was capable of selecting hypo- but not hyperphosphorylated forms of retinoblastoma for degradation. The engineered betaTrCP has been extensively modified to increase its specificity in substrate selection. This optimized protein-knockout system offers a powerful and versatile proteomic tool to dissect diverse functional properties of cellular proteins in somatic cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.