@article{033ec6b62d2844b1b692015d26b022be,
title = "Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities",
abstract = "Non-neuronal optogenetic approaches empower precise regulation of protein dynamics in live cells but often require target-specific protein engineering. To address this challenge, we developed a generalizable light-modulated protein stabilization system (GLIMPSe) to control the intracellular protein level independent of its functionality. We applied GLIMPSe to control two distinct classes of proteins: mitogen-activated protein kinase phosphatase 3 (MKP3), a negative regulator of the extracellular signal-regulated kinase (ERK) pathway, and a constitutively active form of MEK (CA MEK), a positive regulator of the same pathway. Kinetics study showed that light-induced protein stabilization could be achieved within 30 min of blue light stimulation. GLIMPSe enables target-independent optogenetic control of protein activities and therefore minimizes the systematic variation embedded within different photoactivatable proteins. Overall, GLIMPSe promises to achieve light-mediated post-translational stabilization of a wide array of target proteins in live cells.",
keywords = "CA MEK, GLIMPSe, MKP3, degron, optogenetics, protein degradation",
author = "Payel Mondal and Krishnamurthy, {Vishnu V.} and Sharum, {Savanna R.} and Neeka Haack and Huiwen Zhou and Jennifer Cheng and Jing Yang and Kai Zhang",
note = "Research reported in this publication was supported by the School of Molecular and Cellular Biology at UIUC and the National Institute of General Medical Sciences of the National Institutes of Health under Award No. R01GM132438 (K.Z.) and NIH R35 GM131810 (J.Y.). P.M. is grateful to the Dissertation Completion Fellowship at UIUC for support. S.R.S. is grateful to the Westcott Bioscience Fellowship from the Biochemistry Department at UIUC for support. We thank Dr. Tobias Meyer from Stanford University for the gift of PC12 NS1 cells and Dr. Lin-Feng Chen (UIUC) for the gift of HEK293T cells. We also thank Ranajay Mandal from Purdue University for technical support in the construction of the LED lightbox. Research reported in this publication was supported by the School of Molecular and Cellular Biology at UIUC and the National Institute of General Medical Sciences of the National Institutes of Health under Award No. R01GM132438 (K.Z.) and NIH R35 GM131810 (J.Y.). P.M. is grateful to the Dissertation Completion Fellowship at UIUC for support. S.R.S. is grateful to the Westcott Bioscience Fellowship from the Biochemistry Department at UIUC for support. We thank Dr. Tobias Meyer from Stanford University for the gift of PC12 NS1 cells and Dr. Lin-Feng Chen (UIUC) for the gift of HEK293T cells. We also thank Ranajay Mandal from Purdue University for technical support in the construction of the LED lightbox.",
year = "2019",
month = nov,
day = "15",
doi = "10.1021/acssynbio.9b00285",
language = "English (US)",
volume = "8",
pages = "2585--2592",
journal = "ACS synthetic biology",
issn = "2161-5063",
publisher = "American Chemical Society",
number = "11",
}