Atlas of Genetics and Cytogenetics in Oncology and Haematology
RHOB (ras homolog gene family, member B)
| Identity |
| Other names | ARH6 |
| ARHB | |
| H6 | |
| RHOH6 | |
| HGNC | RHOB |
| Location | 2p24.1 |
| Location_base_pair | Starts at 20510316 and ends at 20512682 bp from pter ( according to hg18-Mar_2006). |
| DNA/RNA |
 | |
| Description | The gene encompasses 2,366 bps (chr2:20,510,316-20,512,681); 1 exon. |
| Transcription | The coding sequence (CDS) region is 395.983bp (588 bp) encoding a protein of 196 aa long. |
| Protein |
| Description | Length 196 aa, molecular weight 22123 Da (unprocessed precursor). RhoB protein exists in different geranylgeranylated (RhoB-GG) or farnesylated (RhoB-F) isoforms in cells. |
| Expression | Widely expressed. |
| Localisation | Endosome; Late endosome; late endosomal membrane; cell membrane; Also detected at the nuclear margin and in the nucleus. Prenylation specifies the subcellular location of RHOB. In general, the farnesylated form is localized to the plasma membrane while the geranylgeranylated form is localized to the endosome. |
| Function | Regulator of protein signaling and trafficking: Plays a pivotal role in the dynamic regulation of the actin cytoskeleton. Involved in intracellular protein trafficking of a number of proteins. Targets PRK1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of Akt which promotes endothelial cell survival during vascular development. Identified as a component of outside-in signaling pathways that coordinate Src activation with its translocation to transmembrane receptors. Negative modifier of cancer progression: Affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as RhoB deletion increases tumor formation initiated by Ras mutation. Limits the proliferation of transformed cells by facilitating turnover of oncogene c-Myc. Expression levels are dramatically decreased in lung, head and neck, and brain cancer, when tumors become more aggressive. Modulator of cancer cell apoptosis: Promotes proapoptotic signaling of regulators involved in cell cycle checkpoints, cell adhesion, vesicle trafficking, MAPK signaling, transcription, and immunity. Mediates apoptosis in neoplastically transformed cells after DNA damage. Is essential for apoptosis and antineoplastic activity of farnesyltransferase inhibitors in a mouse model. Is one of the targets of farnesyltransferase inhibitors which are currently under investigation as cancer therapeutics. |
| Homology | Member of the ras gene superfamily; rho family; GTP-binding proteins. The RhoA, RhoB, and RhoC proteins form a closely related subgroup that are about 90% identical in amino acid sequence. The sequences of RHOB are highly-conserved between species (from human to fly). Amino acid sequences of human, mouse and rat are 100% identical while sequence homology between human and chicken is 97% identical. |
| Implicated in |
| Entity | Lung cancer |
| Note | RhoB expression is frequently downregulated in lung cancer by multiple mechanisms. Low or no expression of RhoB is more frequently observed in poorly- or moderately-differentiated adenocarcinomas, and indicative of poor patient prognosis. |
| Entity | Head and neck cancer |
| Note | RhoB expression decreases to undetectable level as tumors become more invasive and poorly differentiated. In contrast, Ki67 (proliferation marker) and RhoA protein levels increase with tumor progression. |
| External links |
| Bibliography |
| A novel ras-related gene family. |
| Madaule P, Axel R |
| Cell. 1985 ; 41 (1) : 31-40. |
| PMID 3888408 |
| Coding sequence of human rho cDNAs clone 6 and clone 9. |
| Chardin P, Madaule P, Tavitian A |
| Nucleic acids research. 1988 ; 16 (6) : page 2717. |
| PMID 3283705 |
| Chromosome localization of human ARH genes, a ras-related gene family. |
| Cannizzaro LA, Madaule P, Hecht F, Axel R, Croce CM, Huebner K |
| Genomics. 1990 ; 6 (2) : 197-203. |
| PMID 2407642 |
| Post-translational modifications of p21rho proteins. |
| Adamson P, Marshall CJ, Hall A, Tilbrook PA |
| The Journal of biological chemistry. 1992 ; 267 (28) : 20033-20038. |
| PMID 1400319 |
| CAAX geranylgeranyl transferase transfers farnesyl as efficiently as geranylgeranyl to RhoB. |
| Armstrong SA, Hannah VC, Goldstein JL, Brown MS |
| The Journal of biological chemistry. 1995 ; 270 (14) : 7864-7868. |
| PMID 7713879 |
| Regulation of epidermal growth factor receptor traffic by the small GTPase rhoB. |
| Gampel A, Parker PJ, Mellor H |
| Current biology : CB. 1999 ; 9 (17) : 955-958. |
| PMID 10508588 |
| RhoB alteration is necessary for apoptotic and antineoplastic responses to farnesyltransferase inhibitors. |
| Liu A, Du W, Liu JP, Jessell TM, Prendergast GC |
| Molecular and cellular biology. 2000 ; 20 (16) : 6105-6113. |
| PMID 10913192 |
| RhoB is required to mediate apoptosis in neoplastically transformed cells after DNA damage. |
| Liu Ax, Cerniglia GJ, Bernhard EJ, Prendergast GC |
| Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (11) : 6192-6197. |
| PMID 11353846 |
| Actin' up: RhoB in cancer and apoptosis. |
| Prendergast GC |
| Nature reviews. Cancer. 2001 ; 1 (2) : 162-168. |
| PMID 11905808 |
| Suppression of rho B expression in invasive carcinoma from head and neck cancer patients. |
| Adnane J, Muro-Cacho C, Mathews L, Sebti SM, Muˆ±oz-Antonia T |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2002 ; 8 (7) : 2225-2232. |
| PMID 12114424 |
| RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development. |
| Adini I, Rabinovitz I, Sun JF, Prendergast GC, Benjamin LE |
| Genes & development. 2003 ; 17 (21) : 2721-2732. |
| PMID 14597666 |
| EGFR, ErbB2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene-mediated transformation. |
| Jiang K, Delarue FL, Sebti SM |
| Oncogene. 2004 ; 23 (5) : 1136-1145. |
| PMID 14647415 |
| Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis. |
| Jiang K, Sun J, Cheng J, Djeu JY, Wei S, Sebti S |
| Molecular and cellular biology. 2004 ; 24 (12) : 5565-5576. |
| PMID 15169915 |
| Farnesyltransferase inhibitors disrupt EGF receptor traffic through modulation of the RhoB GTPase. |
| Wherlock M, Gampel A, Futter C, Mellor H |
| Journal of cell science. 2004 ; 117 (Pt 15) : 3221-3231. |
| PMID 15226397 |
| Loss of RhoB expression in human lung cancer progression. |
| Mazieres J, Antonia T, Daste G, Muro-Cacho C, Berchery D, Tillement V, Pradines A, Sebti S, Favre G |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 ; 10 (8) : 2742-2750. |
| PMID 15102679 |
| RhoB and actin polymerization coordinate Src activation with endosome-mediated delivery to the membrane. |
| Sandilands E, Cans C, Fincham VJ, Brunton VG, Mellor H, Prendergast GC, Norman JC, Superti-Furga G, Frame MC |
| Developmental cell. 2004 ; 7 (6) : 855-869. |
| PMID 15572128 |
| RhoB facilitates c-Myc turnover by supporting efficient nuclear accumulation of GSK-3. |
| Huang M, Kamasani U, Prendergast GC |
| Oncogene. 2006 ; 25 (9) : 1281-1289. |
| PMID 16247449 |
| RhoB in cancer suppression. |
| Huang M, Prendergast GC |
| Histology and histopathology. 2006 ; 21 (2) : 213-218. |
| PMID 16329046 |
| RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line. |
| Sato N, Fukui T, Taniguchi T, Yokoyama T, Kondo M, Nagasaka T, Goto Y, Gao W, Ueda Y, Yokoi K, Minna JD, Osada H, Kondo Y, Sekido Y |
| International journal of cancer. Journal international du cancer. 2007 ; 120 (3) : 543-551. |
| PMID 17096327 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 02-2007 | Minzhou Huang, Lisa D Laury-Kleintop, George Prendergast |
| Citation |
| This paper should be referenced as such : |
| Huang M, Laury-Kleintop LD, Prendergast G . RHOB (ras homolog gene family, member B). Atlas Genet Cytogenet Oncol Haematol. February 2007 . URL : http://AtlasGeneticsOncology.org/Genes/RHOBID42108ch2p24.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Dec 6 17:59:08 2008 |
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