RIPK4 activity in keratinocytes is controlled by the SCF(beta-TrCP) ubiquitin ligase to maintain cortical actin organization.

Tanghe, Giel; Urwyler-Rosselet, Corinne; De Groote, Philippe; Dejardin, Emmanuel; De Bock, Pieter-Jan; Gevaert, Kris; Vandenabeele, Peter; Declercq, Wim

doi:10.1007/s00018-018-2763-6

Article (Scientific journals)

RIPK4 activity in keratinocytes is controlled by the SCF(beta-TrCP) ubiquitin ligase to maintain cortical actin organization.

Tanghe, Giel; Urwyler-Rosselet, Corinne; De Groote, Philippe et al.

2018 • In Cellular and Molecular Life Sciences

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/225683

DOI
10.1007/s00018-018-2763-6

PubMed
29435596

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Keywords :

Degradation; Keratinocytes; PKC; Proteasome; RIPK4; beta-TrCP

Abstract :

[en] 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-kappaB 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.

Disciplines :

Immunology & infectious disease

Author, co-author :

Tanghe, Giel

Urwyler-Rosselet, Corinne

De Groote, Philippe

Dejardin, Emmanuel ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo of Molecular Immunol. and Signal Transduction

De Bock, Pieter-Jan

Gevaert, Kris

Vandenabeele, Peter

Declercq, Wim

Language :

English

Title :

RIPK4 activity in keratinocytes is controlled by the SCF(beta-TrCP) ubiquitin ligase to maintain cortical actin organization.

Publication date :

2018

Journal title :

Cellular and Molecular Life Sciences

ISSN :

1420-682X

eISSN :

1420-9071

Publisher :

Birkhauser Verlag, Switzerland

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 20 June 2018

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