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 language | English (US) |
|---|---|
| Pages (from-to) | 2585-2592 |
| Number of pages | 8 |
| Journal | ACS synthetic biology |
| Volume | 8 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 15 2019 |
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Keywords
- CA MEK
- GLIMPSe
- MKP3
- degron
- optogenetics
- protein degradation
ASJC Scopus subject areas
- Biomedical Engineering
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Repurposing Protein Degradation for Optogenetic Modulation of Protein Activities
AU - Mondal, Payel
AU - Krishnamurthy, Vishnu V.
AU - Sharum, Savanna R.
AU - Haack, Neeka
AU - Zhou, Huiwen
AU - Cheng, Jennifer
AU - Yang, Jing
AU - Zhang, Kai
PY - 2019/11/15
Y1 - 2019/11/15
N2 - 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.
AB - 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.
KW - CA MEK
KW - GLIMPSe
KW - MKP3
KW - degron
KW - optogenetics
KW - protein degradation
UR - http://www.scopus.com/inward/record.url?scp=85074193497&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074193497&partnerID=8YFLogxK
U2 - 10.1021/acssynbio.9b00285
DO - 10.1021/acssynbio.9b00285
M3 - Article
C2 - 31600062
AN - SCOPUS:85074193497
VL - 8
SP - 2585
EP - 2592
JO - ACS Synthetic Biology
JF - ACS Synthetic Biology
SN - 2161-5063
IS - 11
ER -