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PMID: 27875099 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The RhoB small GTPase in physiology and disease.

Small GTPases ·Vol. 9 ·No. 5 ·2018-00-03 ·Pages 384-393

Vega FM, Ridley AJ

Abstract

RhoB is a Rho family GTPase that is highly similar to RhoA and RhoC, yet has distinct functions in cells. Its unique C-terminal region is subject to specific post-translational modifications that confer different localization and functions to RhoB. Apart from the common role with RhoA and RhoC in actin organization and cell migration, RhoB is also implicated in a variety of other cellular processes including membrane trafficking, cell proliferation, DNA-repair and apoptosis. RhoB is not an essential gene in mice, but it is implicated in several physiological and pathological processes. Its multiple roles will be discussed in this review.

Keywords
Rho GTPases RhoB cancer progression development membrane trafficking
MeSH Terms
Amino Acid Sequence Animals Disease Growth and Development Humans Neoplasms/enzymology Neovascularization, Physiologic rhoB GTP-Binding Protein/chemistry,metabolism
Chemicals
rhoB GTP-Binding Protein
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Vega Francisco M ORCID
a Instituto de Biomedicina de Sevilla, IBiS (Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla) , Sevilla , Spain. | b Department of Medical Physiology and Biophysics , Universidad de Sevilla , Sevilla , Spain.
Ridley Anne J ORCID
c Randall Division of Cell and Molecular Biophysics, King's College London , New Hunt's House, Guy's Campus, London , UK.
References (85)
85 references, click to expand
  1. RhoA and RhoC have distinct roles in migration and invasion by acting through different targets.
    J Cell Biol. 2011 May 16;193(4):655-65 PMID: 21576392
  2. RhoB and actin polymerization coordinate Src activation with endosome-mediated delivery to the membrane.
    Dev Cell. 2004 Dec;7(6):855-69 PMID: 15572128
  3. Role of RhoB in the regulation of pulmonary endothelial and smooth muscle cell responses to hypoxia.
    Circ Res. 2012 May 25;110(11):1423-34 PMID: 22539766
  4. ATR/Chk1/Smurf1 pathway determines cell fate after DNA damage by controlling RhoB abundance.
    Nat Commun. 2014 Sep 24;5:4901 PMID: 25249323
  5. Physiological roles of Rho and Rho effectors in mammals.
    Eur J Cell Biol. 2013 Oct-Nov;92 (10-11):303-15 PMID: 24183240
  6. Epigenetic regulation of RhoB loss of expression in lung cancer.
    BMC Cancer. 2007 Nov 30;7:220 PMID: 18047684
  7. RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG.
    J Biol Chem. 1996 Nov 29;271(48):30366-74 PMID: 8939998
  8. Critical role of Rho in cell transformation by oncogenic Ras.
    Oncogene. 1995 Jun 15;10(12):2289-96 PMID: 7784077
  9. Ensembl Genomes 2016: more genomes, more complexity.
    Nucleic Acids Res. 2016 Jan 4;44(D1):D574-80 PMID: 26578574
  10. RhoB loss induces Rac1-dependent mesenchymal cell invasion in lung cells through PP2A inhibition.
    Oncogene. 2016 Apr 7;35(14):1760-9 PMID: 26148238
  11. RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development.
    Genes Dev. 2003 Nov 1;17(21):2721-32 PMID: 14597666
  12. Rho GTPases in cancer cell biology.
    FEBS Lett. 2008 Jun 18;582(14):2093-101 PMID: 18460342
  13. Sp1-driven up-regulation of miR-19a decreases RHOB and promotes pancreatic cancer.
    Oncotarget. 2015 Jul 10;6(19):17391-403 PMID: 26041879
  14. Cyclin B1 is a critical target of RhoB in the cell suicide program triggered by farnesyl transferase inhibition.
    Cancer Res. 2004 Nov 15;64(22):8389-96 PMID: 15548709
  15. Mouse macrophages completely lacking Rho subfamily GTPases (RhoA, RhoB, and RhoC) have severe lamellipodial retraction defects, but robust chemotactic navigation and altered motility.
    J Biol Chem. 2014 Oct 31;289(44):30772-84 PMID: 25213860
  16. RhoB is expressed in migrating neural crest and endocardial cushions of the developing mouse embryo.
    Mech Dev. 2000 Jul;95(1-2):211-4 PMID: 10906464
  17. ROCK I-mediated activation of NF-kappaB by RhoB.
    Cell Signal. 2007 Nov;19(11):2361-9 PMID: 17728102
  18. PRK1 is targeted to endosomes by the small GTPase, RhoB.
    J Biol Chem. 1998 Feb 27;273(9):4811-4 PMID: 9478917
  19. A role for rhoB in the delamination of neural crest cells from the dorsal neural tube.
    Development. 1998 Dec;125(24):5055-67 PMID: 9811589
  20. RhoB is dispensable for mouse development, but it modifies susceptibility to tumor formation as well as cell adhesion and growth factor signaling in transformed cells.
    Mol Cell Biol. 2001 Oct;21(20):6906-12 PMID: 11564874
  21. Expression of RhoB in the developing Xenopus laevis embryo.
    Gene Expr Patterns. 2007 Jan;7(3):282-8 PMID: 17049930
  22. The neddylation-cullin 2-RBX1 E3 ligase axis targets tumor suppressor RhoB for degradation in liver cancer.
    Mol Cell Proteomics. 2015 Mar;14(3):499-509 PMID: 25540389
  23. RhoB regulates endosome transport by promoting actin assembly on endosomal membranes through Dia1.
    J Cell Sci. 2005 Jun 15;118(Pt 12):2661-70 PMID: 15944396
  24. Regulation of Ras-related RhoB protein expression during the cell cycle.
    Oncogene. 1995 May 18;10(10):1935-45 PMID: 7539118
  25. Regulation of small GTPases by GEFs, GAPs, and GDIs.
    Physiol Rev. 2013 Jan;93(1):269-309 PMID: 23303910
  26. Activation of the RhoB signaling pathway by thyroid hormone receptor β in thyroid cancer cells.
    PLoS One. 2014 Dec 30;9(12):e116252 PMID: 25548921
  27. Geranylgeranylated, but not farnesylated, RhoB suppresses Ras transformation of NIH-3T3 cells.
    Exp Cell Res. 2005 Apr 1;304(2):354-64 PMID: 15748883
  28. RhoB in cancer suppression.
    Histol Histopathol. 2006 Feb;21(2):213-8 PMID: 16329046
  29. Rho GTPase isoforms in cell motility: Don't fret, we have FRET.
    Cell Adh Migr. 2014;8(6):526-34 PMID: 25482645
  30. Intracellular localization of the P21rho proteins.
    J Cell Biol. 1992 Nov;119(3):617-27 PMID: 1383236
  31. RhoB plays an essential role in CXCR2 sorting decisions.
    J Cell Sci. 2007 May 1;120(Pt 9):1559-71 PMID: 17405813
  32. MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells.
    PLoS One. 2011 Feb 10;6(2):e16979 PMID: 21347332
  33. Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis.
    Mol Cell Biol. 2004 Jun;24(12):5565-76 PMID: 15169915
  34. RhoB regulates uPAR signalling.
    J Cell Sci. 2012 May 15;125(Pt 10):2369-80 PMID: 22366462
  35. Cdc42 and RhoB activation are required for mannose receptor-mediated phagocytosis by human alveolar macrophages.
    Mol Biol Cell. 2005 Feb;16(2):824-34 PMID: 15574879
  36. Genetic response to farnesyltransferase inhibitors: proapoptotic targets of RhoB.
    Cancer Biol Ther. 2003 May-Jun;2(3):273-80 PMID: 12878865
  37. Rho GTPase function in tumorigenesis.
    Biochim Biophys Acta. 2009 Dec;1796(2):91-8 PMID: 19327386
  38. RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border.
    J Cell Biol. 2016 May 9;213(3):385-402 PMID: 27138256
  39. Both farnesylated and geranylgeranylated RhoB inhibit malignant transformation and suppress human tumor growth in nude mice.
    J Biol Chem. 2000 Jun 16;275(24):17974-8 PMID: 10770919
  40. RhoB deficiency in thymic medullary epithelium leads to early thymic atrophy.
    Int Immunol. 2011 Oct;23(10):593-600 PMID: 21865151
  41. Spatiotemporal analysis of RhoA/B/C activation in primary human endothelial cells.
    Sci Rep. 2016 May 05;6:25502 PMID: 27147504
  42. Rnd3 induces stress fibres in endothelial cells through RhoB.
    Biol Open. 2013 Feb 15;2(2):210-6 PMID: 23430146
  43. Small GTP-binding protein RhoB is expressed in glial Müller cells in the vertebrate retina.
    J Comp Neurol. 2006 Feb 20;494(6):976-85 PMID: 16385489
  44. Phosphorylation of RhoB by CK1 impedes actin stress fiber organization and epidermal growth factor receptor stabilization.
    Exp Cell Res. 2008 Sep 10;314(15):2811-21 PMID: 18590726
  45. Activation of RhoB by hypoxia controls hypoxia-inducible factor-1alpha stabilization through glycogen synthase kinase-3 in U87 glioblastoma cells.
    Cancer Res. 2006 Jan 1;66(1):482-9 PMID: 16397264
  46. SmgGDS is a guanine nucleotide exchange factor that specifically activates RhoA and RhoC.
    J Biol Chem. 2011 Apr 8;286(14):12141-8 PMID: 21242305
  47. Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain.
    J Proteome Res. 2008 Jan;7(1):311-8 PMID: 18034455
  48. XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC.
    J Biol Chem. 2002 Nov 8;277(45):42964-72 PMID: 12221096
  49. The transcriptional control of trunk neural crest induction, survival, and delamination.
    Dev Cell. 2005 Feb;8(2):179-92 PMID: 15691760
  50. Overexpression of Snail family members highlights their ability to promote chick neural crest formation.
    Development. 2002 Apr;129(7):1583-93 PMID: 11923196
  51. RhoB is involved in lipopolysaccharide-induced inflammation in mouse in vivo and in vitro.
    J Physiol Biochem. 2013 Jun;69(2):189-97 PMID: 22869204
  52. Rho protein crosstalk: another social network?
    Trends Cell Biol. 2011 Dec;21(12):718-26 PMID: 21924908
  53. Critical functions of RhoB in support of glioblastoma tumorigenesis.
    Neuro Oncol. 2015 Apr;17(4):516-25 PMID: 25216671
  54. Farnesyltransferase inhibitors disrupt EGF receptor traffic through modulation of the RhoB GTPase.
    J Cell Sci. 2004 Jul 1;117(Pt 15):3221-31 PMID: 15226397
  55. EGFR, ErbB2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene-mediated transformation.
    Oncogene. 2004 Feb 5;23(5):1136-45 PMID: 14647415
  56. RhoB controls endothelial cell morphogenesis in part via negative regulation of RhoA.
    Vasc Cell. 2012 Feb 08;4:1 PMID: 22316440
  57. RhoB is required to mediate apoptosis in neoplastically transformed cells after DNA damage.
    Proc Natl Acad Sci U S A. 2001 May 22;98(11):6192-7 PMID: 11353846
  58. RhoB promotes γH2AX dephosphorylation and DNA double-strand break repair.
    Mol Cell Biol. 2014 Aug;34(16):3144-55 PMID: 24912678
  59. Dual inhibition of histone deacetylases and phosphoinositide 3-kinases: effects on Burkitt lymphoma cell growth and migration.
    J Leukoc Biol. 2016 Apr;99(4):569-78 PMID: 26561567
  60. RhoB and the mammalian Diaphanous-related formin mDia2 in endosome trafficking.
    Exp Cell Res. 2007 Feb 1;313(3):560-71 PMID: 17198702
  61. Reactivation of suppressed RhoB is a critical step for the inhibition of anaplastic thyroid cancer growth.
    Cancer Res. 2009 Feb 15;69(4):1536-44 PMID: 19208833
  62. RhoB regulates the function of macrophages in the hypoxia-induced inflammatory response.
    Cell Mol Immunol. 2017 Mar;14 (3):265-275 PMID: 26388235
  63. RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production.
    Cell Cycle. 2015;14(17):2748-63 PMID: 26114383
  64. RhoB regulates cell migration through altered focal adhesion dynamics.
    Open Biol. 2012 May;2(5):120076 PMID: 22724071
  65. RhoA-GDP regulates RhoB protein stability. Potential involvement of RhoGDIalpha.
    J Biol Chem. 2008 Aug 1;283(31):21588-98 PMID: 18524772
  66. Rho GTPase signalling in cell migration.
    Curr Opin Cell Biol. 2015 Oct;36:103-12 PMID: 26363959
  67. RhoA, RhoB and RhoC have different roles in cancer cell migration.
    J Microsc. 2013 Sep;251(3):242-9 PMID: 23488932
  68. RhoB mRNA is stabilized by HuR after UV light.
    Oncogene. 2005 Jan 13;24(3):502-11 PMID: 15543229
  69. miR-21 targets the tumor suppressor RhoB and regulates proliferation, invasion and apoptosis in colorectal cancer cells.
    FEBS Lett. 2011 Oct 3;585(19):2998-3005 PMID: 21872591
  70. RhoB affects macrophage adhesion, integrin expression and migration.
    Exp Cell Res. 2007 Oct 1;313(16):3505-16 PMID: 17692842
  71. RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription.
    Nat Commun. 2013;4:2824 PMID: 24280686
  72. Rho isoforms have distinct and specific functions in the process of epithelial to mesenchymal transition in renal proximal tubular cells.
    Cell Signal. 2009 Oct;21(10):1522-31 PMID: 19477269
  73. Regulation of epidermal growth factor receptor traffic by the small GTPase rhoB.
    Curr Biol. 1999 Sep 9;9(17):955-8 PMID: 10508588
  74. Histone deacetylase 1 represses the small GTPase RhoB expression in human nonsmall lung carcinoma cell line.
    Oncogene. 2003 Sep 18;22(40):6204-13 PMID: 13679859
  75. RhoB upregulation leads to either apoptosis or cytostasis through differential target selection.
    Endocr Relat Cancer. 2015 Oct;22(5):777-92 PMID: 26206775
  76. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses.
    Curr Protoc Bioinformatics. 2016 Jun 20;54:1.30.1-1.30.33 PMID: 27322403
  77. Differential binding of RhoA, RhoB, and RhoC to protein kinase C-related kinase (PRK) isoforms PRK1, PRK2, and PRK3: PRKs have the highest affinity for RhoB.
    Biochemistry. 2013 Nov 12;52(45):7999-8011 PMID: 24128008
  78. LSox5 regulates RhoB expression in the neural tube and promotes generation of the neural crest.
    Development. 2004 Sep;131(18):4455-65 PMID: 15306568
  79. RhoB links PDGF signaling to cell migration by coordinating activation and localization of Cdc42 and Rac.
    J Cell Biochem. 2011 Jun;112(6):1572-84 PMID: 21344485
  80. A molecular ruler regulates cytoskeletal remodelling by the Rho kinases.
    Nat Commun. 2015 Dec 01;6:10029 PMID: 26620183
  81. EphA4, RhoB and the molecular development of feather buds are maintained by the integrity of the actin cytoskeleton.
    Dev Biol. 2004 Jun 1;270(1):94-105 PMID: 15136143
  82. Toward understanding RhoGTPase specificity: structure, function and local activation.
    Small GTPases. 2014;5(2):6 PMID: 25483298
  83. The Rho GTPase RhoB regulates cadherin expression and epithelial cell-cell interaction.
    Cell Commun Signal. 2015 Jan 29;13:6 PMID: 25630770
  84. The nuclear guanine nucleotide exchange factors Ect2 and Net1 regulate RhoB-mediated cell death after DNA damage.
    PLoS One. 2011 Feb 23;6(2):e17108 PMID: 21373644
  85. The small GTPase RhoB regulates TNFα signaling in endothelial cells.
    PLoS One. 2013 Sep 26;8(9):e75031 PMID: 24086429
Article Info
Journal
Small GTPases
Abbr.
Small GTPases
ISSN
2154-1256
DOI
10.1080/21541248.2016.1253528
Published
2018-00-03
Epub
2016-00-22
Pages
384-393
Language
English
Region
United States
NLM ID
101530974
PMCID
PMC5997158
Subset
IM
Grants
Cancer Research UK · C6620/A15961 · United Kingdom
External Links
PubMed source DOI: 10.1080/21541248.2016.1253528 PMC Full Text
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