{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRhoB is a small GTPase belonging to the Ras superfamily that plays pivotal roles in the regulation of the actin cytoskeleton, vesicle transport, and receptor trafficking. Its expression and activity are tightly controlled by post‐translational modifications – such as farnesylation versus geranylgeranylation – and by metabolic cues (for example, mevalonate depletion increases de novo synthesis and stability of RhoB), thereby influencing its cellular localization and function in stress responses and cell signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to other Rho isoforms with predominantly pro‐oncogenic roles, RhoB often exerts tumor‐suppressive functions. Oncogenic signals (such as those driven by mutant Ras or activated EGFR) have been shown to suppress RhoB transcription, while specific guanine nucleotide exchange factors can preferentially activate RhoB over paralogues like RhoC. RhoB’s localization to endosomal compartments further enables it to delay receptor (e.g. EGFR) trafficking and thereby modulate cell proliferation and survival, with evidence also indicating that RhoB can limit the growth of transformed cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in controlling proliferation, RhoB is a critical mediator of cellular stress responses. Upon exposure to genotoxic stress such as ultraviolet B irradiation or chemotherapeutic agents, RhoB is rapidly activated, thereby engaging downstream signaling cascades that modulate AKT phosphorylation and promote actin reorganization through effectors like the formin mDia2. RhoB activation contributes to apoptosis and influences the sensitivity of cancer cells to ionizing radiation and farnesyltransferase inhibitors by integrating signals from integrin‐linked kinase pathways and other stress‐responsive effectors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have further illuminated the regulatory network surrounding RhoB. MicroRNAs – notably miR‐21 – target the 3′ untranslated region of RhoB mRNA, thereby down‐regulating its expression and promoting cell invasion and metastasis; conversely, loss of these miRNAs leads to increased RhoB levels that inhibit migratory behavior. Natural compounds, such as aloe emodin, have been demonstrated to suppress RhoB expression and thereby impact migration and angiogenesis, while epigenetic mechanisms (for example, those linking RASSF1A inactivation with altered RhoB activity) modulate its effects on tumor invasiveness. In addition, RhoB has been implicated in immune cell function—regulating alveolar macrophage phagocytosis and even modulating T cell receptor activation through its redistribution to membrane-associated regulatory proteins—and in the pathogenesis of vascular conditions such as pulmonary hypertension and inflammatory lung injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A x Liu, W Du, J P Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.20.16.6105-6113.2000"}], "href": "https://doi.org/10.1128/MCB.20.16.6105-6113.2000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10913192"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10913192"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sarah A Holstein, Christine L Wohlford-Lenane, Raymond J Hohl "}, {"type": "b", "children": [{"type": "t", "text": "Consequences of mevalonate depletion. Differential transcriptional, translational, and post-translational up-regulation of Ras, Rap1a, RhoA, AND RhoB."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111369200"}], "href": "https://doi.org/10.1074/jbc.M111369200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11788600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11788600"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "G C Prendergast "}, {"type": "b", "children": [{"type": "t", "text": "Actin' up: RhoB in cancer and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Rev Cancer (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/35101096"}], "href": "https://doi.org/10.1038/35101096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11905808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11905808"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "William T Arthur, Shawn M Ellerbroek, Channing J Der, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M207401200"}], "href": "https://doi.org/10.1074/jbc.M207401200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12221096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12221096"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kun Jiang, Frederic L Delarue, Saïd M Sebti "}, {"type": "b", "children": [{"type": "t", "text": "EGFR, ErbB2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene-mediated transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1207236"}], "href": "https://doi.org/10.1038/sj.onc.1207236"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14647415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14647415"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Julien Mazieres, Teresita Antonia, Ghislaine Daste, et al. 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