{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRHOV, also known as Chp or WRCH2, is an atypical member of the Rho GTPase family characterized by unique structural features including a proline‐rich N-terminal region and noncanonical C-terminal sequences that govern its membrane association and posttranslational modifications. It shares significant identity with other Rho GTPases such as CDC42 while incorporating distinct regulatory domains that modulate its subcellular localization and effector interactions. Notably, RHOV directly engages p21-activated kinases (PAKs), including Pak1 and Pak6, via its effector domain—with specific residues being critical for binding—and can even trigger autophosphorylation-induced, ubiquitin-dependent degradation of these kinases. In addition, its N-terminal proline-rich motif mediates binding to SH3 domain–containing adaptor proteins (GRB2 and NCK2) and is subject to regulatory phosphorylation by PKA, thereby fine-tuning its signaling output."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nElevated expression of RHOV has been strongly implicated in driving malignant phenotypes in several human cancers. In lung adenocarcinoma, for example, increased RHOV levels promote cell proliferation, migration, and invasion by activating the JNK/c-Jun signaling cascade and inducing epithelial-to-mesenchymal transition—contributing to metastasis and poor overall survival. Similar oncogenic activities have been observed in non–small‐cell lung cancer and triple-negative breast cancer, where RHOV interacts with phosphorylated EGFR in a GRB2-dependent manner; pan-cancer analyses further reveal that RHOV dysregulation correlates with clinical outcomes, suggesting that its function may be context dependent with potential tumor-suppressive effects in certain settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in tumorigenesis, RHOV is also important in physiological processes and host–pathogen interactions. During embryonic development, RHOV is transiently induced via canonical Wnt signaling in the neural crest, where it contributes to the epithelial-to-mesenchymal transition essential for normal cell differentiation. Moreover, recent evidence has uncovered a proviral role for RHOV in early flavivirus infections (such as Zika virus), where an intact GTPase cycle is necessary to facilitate viral entry—expanding the functional repertoire of this atypical GTPase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masaru Katoh "}, {"type": "b", "children": [{"type": "t", "text": "Molecular cloning and characterization of WRCH2 on human chromosome 15q15."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11956592"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11956592"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Emily J Chenette, Arie Abo, Channing J Der "}, {"type": "b", "children": [{"type": "t", "text": "Critical and distinct roles of amino- and carboxyl-terminal sequences in regulation of the biological activity of the Chp atypical Rho GTPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M411300200"}], "href": "https://doi.org/10.1074/jbc.M411300200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15664990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15664990"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Monika Weisz Hubsman, Natalia Volinsky, Edward Manser, et al. 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