Advanced search
1 file | 2.13 MB

RIPK4 activity in keratinocytes is controlled by the SCFβ-TrCP ubiquitin ligase to maintain cortical actin organization

Author
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

Downloads

    • full text
    • |
    • UGent only
    • |
    • binary/octet-stream
    • |
    • 2.13 MB

Citation

Please use this url to cite or link to this publication:

Chicago
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.
APA
Tanghe, G., Urwyler, C., De Groote, P., Dejardin, E., De Bock, P.-J., Gevaert, K., Vandenabeele, P., et al. (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.
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.
MLA
Tanghe, Giel, Corinne Urwyler, Philippe De Groote, et al. “RIPK4 Activity in Keratinocytes Is Controlled by the SCFβ-TrCP Ubiquitin Ligase to Maintain Cortical Actin Organization.” CELLULAR AND MOLECULAR LIFE SCIENCES 75.15 (2018): 2827–2841. Print.
@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},
  keyword      = {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 SCF\ensuremath{\beta}-TrCP ubiquitin ligase to maintain cortical actin organization},
  url          = {http://dx.doi.org/10.1007/s00018-018-2763-6},
  volume       = {75},
  year         = {2018},
}

Altmetric
View in Altmetric
Web of Science
Times cited: