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

Fingerprint

Optogenetics
Proteolysis
Modulation
Proteins
Degradation
Light
Stabilization
Dual Specificity Phosphatase 6
Protein Engineering
Protein Array Analysis
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Phosphatases

Keywords

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

ASJC Scopus subject areas

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

Cite this

Mondal, P., Krishnamurthy, V. V., Sharum, S. R., Haack, N., Zhou, H., Cheng, 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

Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities. / Mondal, Payel; Krishnamurthy, Vishnu V.; Sharum, Savanna R.; Haack, Neeka; Zhou, Huiwen; Cheng, Jennifer; Yang, Jing; Zhang, Kai.

In: ACS synthetic biology, Vol. 8, No. 11, 15.11.2019, p. 2585-2592.

Research output: Contribution to journalArticle

Mondal, P, Krishnamurthy, VV, Sharum, SR, Haack, N, Zhou, H, Cheng, J, Yang, J & Zhang, K 2019, 'Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities', ACS synthetic biology, vol. 8, no. 11, pp. 2585-2592. https://doi.org/10.1021/acssynbio.9b00285
Mondal P, Krishnamurthy VV, Sharum SR, Haack N, Zhou H, Cheng J et al. Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities. ACS synthetic biology. 2019 Nov 15;8(11):2585-2592. https://doi.org/10.1021/acssynbio.9b00285
Mondal, Payel ; Krishnamurthy, Vishnu V. ; Sharum, Savanna R. ; Haack, Neeka ; Zhou, Huiwen ; Cheng, Jennifer ; Yang, Jing ; Zhang, Kai. / Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities. In: ACS synthetic biology. 2019 ; Vol. 8, No. 11. pp. 2585-2592.
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