Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities

Payel Mondal, Vishnu V. Krishnamurthy, Savanna R. Sharum, Neeka Haack, Huiwen Zhou, Jennifer Cheng, Jing Yang, Kai Zhang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2585-2592
Number of pages8
JournalACS synthetic biology
Volume8
Issue number11
DOIs
StatePublished - Nov 15 2019

Keywords

  • CA MEK
  • GLIMPSe
  • MKP3
  • degron
  • optogenetics
  • protein degradation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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  • Cite this

    Mondal, P., Krishnamurthy, V. V., Sharum, S. R., Haack, N., Zhou, H., Cheng, J., Yang, J., & Zhang, K. (2019). Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities. ACS synthetic biology, 8(11), 2585-2592. https://doi.org/10.1021/acssynbio.9b00285