RIPK4 activity in keratinocytes is controlled by the SCFβ-TrCP ubiquitin ligase to maintain cortical actin organization
- Author
- Giel Tanghe (UGent) , Corinne Urwyler (UGent) , Philippe De Groote (UGent) , Emmanuel Dejardin, Pieter-Jan De Bock, Kris Gevaert (UGent) , Peter Vandenabeele (UGent) and Wim Declercq (UGent)
- Organization
- Abstract
- RIPK4 is a key player in epidermal differentiation and barrier formation. RIPK4 signaling pathways controlling keratinocyte proliferation and differentiation depend on its kinase activity leading to Dvl2, Pkp1 and IRF6 phosphorylation and NF-kappa B activation. However, the mechanism regulating RIPK4 activity levels remains elusive. We show that cultured keratinocytes display constitutive active phosphorylated RIPK4 while PKC signaling can trigger RIPK4 activation in various non-keratinocyte cell lines, in which RIPK4 is present in a non-phosphorylated state. Interestingly, we identified the SCF beta-TrCP ubiquitin E3 ligase complex responsible for regulating the active RIPK4 protein level. The SCF beta-TrCP complex binds to a conserved phosphodegron motif in the intermediate domain of RIPK4, subsequently leading to K48-linked ubiquitinylation and degradation. The recruitment of beta-TrCP is dependent on RIPK4 activation and trans-autophosphorylation. beta-TrCP knock-down resulted in RIPK4-dependent formation of actin stress fibers, cell scattering and increased cell motility, suggesting that tight control of RIPK4 activity levels is crucial to maintain cell shape and behavior in keratinocytes.
- Keywords
- RIPK4, beta-TrCP, Keratinocytes, Proteasome, Degradation, PKC, NF-KAPPA-B, C-ASSOCIATED KINASE, PROTEIN-KINASE, DIFFERENTIATION, SKIN, CELL, PKK, ACTIVATION, MUTATIONS, STABILITY
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8566722
- MLA
- Tanghe, Giel, et al. “RIPK4 Activity in Keratinocytes Is Controlled by the SCFβ-TrCP Ubiquitin Ligase to Maintain Cortical Actin Organization.” CELLULAR AND MOLECULAR LIFE SCIENCES, vol. 75, no. 15, 2018, pp. 2827–41, doi:10.1007/s00018-018-2763-6.
- APA
- Tanghe, G., Urwyler, C., De Groote, P., Dejardin, E., De Bock, P.-J., Gevaert, K., … Declercq, W. (2018). RIPK4 activity in keratinocytes is controlled by the SCFβ-TrCP ubiquitin ligase to maintain cortical actin organization. CELLULAR AND MOLECULAR LIFE SCIENCES, 75(15), 2827–2841. https://doi.org/10.1007/s00018-018-2763-6
- Chicago author-date
- Tanghe, Giel, Corinne Urwyler, Philippe De Groote, Emmanuel Dejardin, Pieter-Jan De Bock, Kris Gevaert, Peter Vandenabeele, and Wim Declercq. 2018. “RIPK4 Activity in Keratinocytes Is Controlled by the SCFβ-TrCP Ubiquitin Ligase to Maintain Cortical Actin Organization.” CELLULAR AND MOLECULAR LIFE SCIENCES 75 (15): 2827–41. https://doi.org/10.1007/s00018-018-2763-6.
- Chicago author-date (all authors)
- Tanghe, Giel, Corinne Urwyler, Philippe De Groote, Emmanuel Dejardin, Pieter-Jan De Bock, Kris Gevaert, Peter Vandenabeele, and Wim Declercq. 2018. “RIPK4 Activity in Keratinocytes Is Controlled by the SCFβ-TrCP Ubiquitin Ligase to Maintain Cortical Actin Organization.” CELLULAR AND MOLECULAR LIFE SCIENCES 75 (15): 2827–2841. doi:10.1007/s00018-018-2763-6.
- Vancouver
- 1.Tanghe G, Urwyler C, De Groote P, Dejardin E, De Bock P-J, Gevaert K, et al. RIPK4 activity in keratinocytes is controlled by the SCFβ-TrCP ubiquitin ligase to maintain cortical actin organization. CELLULAR AND MOLECULAR LIFE SCIENCES. 2018;75(15):2827–41.
- IEEE
- [1]G. Tanghe et al., “RIPK4 activity in keratinocytes is controlled by the SCFβ-TrCP ubiquitin ligase to maintain cortical actin organization,” CELLULAR AND MOLECULAR LIFE SCIENCES, vol. 75, no. 15, pp. 2827–2841, 2018.
@article{8566722,
abstract = {{RIPK4 is a key player in epidermal differentiation and barrier formation. RIPK4 signaling pathways controlling keratinocyte proliferation and differentiation depend on its kinase activity leading to Dvl2, Pkp1 and IRF6 phosphorylation and NF-kappa B activation. However, the mechanism regulating RIPK4 activity levels remains elusive. We show that cultured keratinocytes display constitutive active phosphorylated RIPK4 while PKC signaling can trigger RIPK4 activation in various non-keratinocyte cell lines, in which RIPK4 is present in a non-phosphorylated state. Interestingly, we identified the SCF beta-TrCP ubiquitin E3 ligase complex responsible for regulating the active RIPK4 protein level. The SCF beta-TrCP complex binds to a conserved phosphodegron motif in the intermediate domain of RIPK4, subsequently leading to K48-linked ubiquitinylation and degradation. The recruitment of beta-TrCP is dependent on RIPK4 activation and trans-autophosphorylation. beta-TrCP knock-down resulted in RIPK4-dependent formation of actin stress fibers, cell scattering and increased cell motility, suggesting that tight control of RIPK4 activity levels is crucial to maintain cell shape and behavior in keratinocytes.}},
author = {{Tanghe, Giel and Urwyler, Corinne and De Groote, Philippe and Dejardin, Emmanuel and De Bock, Pieter-Jan and Gevaert, Kris and Vandenabeele, Peter and Declercq, Wim}},
issn = {{1420-682X}},
journal = {{CELLULAR AND MOLECULAR LIFE SCIENCES}},
keywords = {{RIPK4,beta-TrCP,Keratinocytes,Proteasome,Degradation,PKC,NF-KAPPA-B,C-ASSOCIATED KINASE,PROTEIN-KINASE,DIFFERENTIATION,SKIN,CELL,PKK,ACTIVATION,MUTATIONS,STABILITY}},
language = {{eng}},
number = {{15}},
pages = {{2827--2841}},
title = {{RIPK4 activity in keratinocytes is controlled by the SCFβ-TrCP ubiquitin ligase to maintain cortical actin organization}},
url = {{http://doi.org/10.1007/s00018-018-2763-6}},
volume = {{75}},
year = {{2018}},
}
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