Phosphorylation of RhoB by CK1 impedes actin stress fiber organization and epidermal growth factor receptor stabilization

Tillement, Vanessa; Lajoie‐Mazenc, Isabelle; Casanova, Anne; Froment, Carine; Pénary, Marie; Tovar, Daniel; Marquez, Rodolfo; Monsarrat, Bernard; Favre, Gilles; Pradines, Anne

doi:10.1016/j.yexcr.2008.06.011

Cited by 26 publications

(18 citation statements)

References 67 publications

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“…In addition, RHOB has been shown to regulate cell shape, migration, and adhesion (30,31). RHOB-null macrophage cells migrated faster than wild-type cells on fibronectin, which correlates with reduced adhesion, possibly due to a reduction in the integrin/RHOB signaling pathway and induction of cofilin (24).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-21 Promotes an In vitro Metastatic Phenotype by Targeting the Tumor Suppressor RHOB

Connolly

Doorslaer

Rogler

et al. 2010

Molecular Cancer Research

103

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Metastasis is a multistep process that involves the deregulation of oncogenes and tumor suppressors beyond changes required for primary tumor formation. RHOB is known to have tumor suppressor activity, and its knockdown is associated with more aggressive tumors as well as changes in cell shape, migration, and adhesion. This study shows that oncogenic microRNA, miR-21, represses RHOB expression by directly targeting the 3′ untranslated region. Loss of miR-21 is associated with an elevation of RHOB in hepatocellular carcinoma cell lines Huh-7 and HepG2 and in the metastatic breast cancer cell line MDA-MB-231. Using in vitro models of distinct stages of metastasis, we showed that loss of miR-21 also causes a reduction in migration, invasion, and cell elongation. The reduction in migration and cell elongation can be mimicked by overexpression of RHOB. Furthermore, changes in miR-21 expression lead to alterations in matrix metalloproteinase-9 activity. Therefore, we conclude that miR-21 promotes multiple components of the metastatic phenotype in vitro by regulating several important tumor suppressors, including RHOB. Mol Cancer Res; 8(5); 691-700. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Overexpression of miR-21 Promotes an In vitro Metastatic Phenotype by Targeting the Tumor Suppressor RHOB

Connolly

Doorslaer

Rogler

et al. 2010

Molecular Cancer Research

103

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“…Protects GTP-bound RhoA from proteasome-mediated degradation 128 • ERK2 -required for FBXL19-dependent RhoA degradation 47 • SLK → S188 -might inhibit RhoA activity 139 • # SMURF1 → K6, K7 and K51 -proteasomal degradation 48,49,51,140 • § SCF FBXL19 → K135 -proteasomal degradation in an ERK-dependent manner 47 • CUL3 BACURD -proteasomal degradation of GDP-bound inactive RhoA 52 • SCF FBXW7 -proteasomal degradation 141 RhoB CK1 → S185 -increases GDP-bound inactive form 142 • CUL2 RBX1 -proteasomal degradation leading to liver carcinogenesis 143 • SMURF1 → K6 and K7 -degradation as part of DNA damage response pathway. RhoB abundance controls cell fate in response to DNA damage 56 RhoC AKT → S73 -required for downstream signalling and mediates increased breast cancer cell invasiveness 144 --…”

Section: Rhoamentioning

confidence: 99%

Regulating Rho GTPases and their regulators

Hodge

Ridley²

2016

Nat Rev Mol Cell Biol

734

657

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Rho GTPases regulate cytoskeletal and cell adhesion dynamics and thereby coordinate a wide range of cellular processes, including cell migration, cell polarity and cell cycle progression. Most Rho GTPases cycle between a GTP-bound active conformation and a GDP-bound inactive conformation to regulate their ability to activate effector proteins and to elicit cellular responses. However, it has become apparent that Rho GTPases are regulated by post-translational modifications and the formation of specific protein complexes, in addition to GTP-GDP cycling. The canonical regulators of Rho GTPases - guanine nucleotide exchange factors, GTPase-activating proteins and guanine nucleotide dissociation inhibitors - are regulated similarly, creating a complex network of interactions to determine the precise spatiotemporal activation of Rho GTPases.

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“…Where indicated, glucose was removed or 0.3 mM tert-butyl-hydroperoxide [TBOOH] (Sigma, Schnelldorf, Germany) was added. The CK1 inhibitors D4476 (4-(4-(2,3-Dihydrobenzo [1,4]dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl)benzamide) (Calbiochem, Bad Soden, Germany) and (R)-DRF053 dihydrochloride (Tocris, Bristol, UK) and the CK1 activator pyrvinium pamoate (6-(Dimethylamino)-2-[2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl) ethenyl] -1-methyl-4,4'-methylene-bis [3-hydroxy-2-naphthalenecarboxylate] (2:1)-quinolinium) (Sigma, Schnelldorf, Germany) were used at the indicated concentrations. D4476, (R)-DRF053 and pyrvinium pamoate were solubilized in DMSO (Calbiochem).…”

Section: Erythrocytes Solutions and Chemicalsmentioning

confidence: 99%

Protein Kinase CK1α Regulates Erythrocyte Survival

Zelenak¹,

Eberhard²,

Jilani³

et al. 2012

Cell Physiol Biochem

112

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Protein kinase CK1 (casein kinase 1) isoforms are involved in the regulation of various physiological functions including apoptosis. The specific CK1 inhibitor D4476 may either inhibit or foster apoptosis. Similar to apoptosis of nucleated cells, eryptosis, the suicidal death of erythrocytes, is paralleled by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include increase of cytosolic Ca²⁺ activity following energy depletion (removal of glucose) or oxidative stress (exposure to the oxidant tert-butyl hydroperoxide [TBOOH]). Western blotting was utilized to verify that erythrocytes express the protein kinase CK1α, and FACS analysis to determine whether the CK1 inhibitor D4476 and CK1α activator pyrvinium pamoate modify forward scatter (reflecting cell volume), annexin V binding (reflecting phosphatidylserine exposure), and Fluo3 fluorescence (reflecting cytosolic Ca²⁺ activity). As a result, both, human and murine erythrocytes express CK1 isoform α. Glucose depletion (48 hours) and exposure to 0.3 mM TBOOH (30 minutes) both decreased forward scatter, increased annexin V binding and increased Fluo3 fluorescence. CK1 inhibitor D4476 (10 µM) significantly blunted the decrease in forward scatter, the increase in annexin V binding and the increase in Fluo 3 fluorescence. (R)-DRF053, another CK1 inhibitor, similarly blunted the increase in annexin V binding upon glucose depletion. The CK1α specific activator pyrvinium pamoate (10 µM) significantly enhanced the increase in annexin V binding and Fluo3 fluorescence upon glucose depletion and TBOOH exposure. In the presence of glucose, pyrvinium pamoate slightly but significantly increased Fluo3 fluorescence. In conclusion, CK1 isoform α participates in the regulation of erythrocyte programmed cell death by modulating cytosolic Ca²⁺ activity.

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Phosphorylation of RhoB by CK1 impedes actin stress fiber organization and epidermal growth factor receptor stabilization

Cited by 26 publications

References 67 publications

Overexpression of miR-21 Promotes an In vitro Metastatic Phenotype by Targeting the Tumor Suppressor RHOB

Overexpression of miR-21 Promotes an In vitro Metastatic Phenotype by Targeting the Tumor Suppressor RHOB

Regulating Rho GTPases and their regulators

Protein Kinase CK1α Regulates Erythrocyte Survival

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