title: A design principle underlying the paradoxical roles of E3 ubiquitin ligases.
abstract: E3 ubiquitin ligases are important cellular components that determine the specificity of proteolysis in the ubiquitin-proteasome system. However, an increasing number of studies have indicated that E3 ubiquitin ligases also participate in transcription. Intrigued by the apparently paradoxical functions of E3 ubiquitin ligases in both proteolysis and transcriptional activation, we investigated the underlying design principles using mathematical modeling. We found that the antagonistic functions integrated in E3 ubiquitin ligases can prevent any undesirable sustained activation of downstream genes when E3 ubiquitin ligases are destabilized by unexpected perturbations. Interestingly, this design principle of the system is similar to the operational principle of a safety interlock device in engineering systems, which prevents a system from abnormal operation unless stability is guaranteed.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Republic of Korea.
authors.forename: Daewon
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Republic of Korea.
authors.forename: Minjin
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Republic of Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D003198:Computer Simulation; D025461:Feedback, Physiological; D006801:Humans; D008954:Models, Biological; D059748:Proteolysis; D015398:Signal Transduction; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D057149:Ubiquitinated Proteins / Q000502:physiology
chemical_list: D057149:Ubiquitinated Proteins; D044767:Ubiquitin-Protein Ligases