RAC3
Ras-related C3 botulinum toxin substrate 3 (Rac3) is a G protein that in humans is encoded by the RAC3 gene.[5] It is an important component of intracellular signalling pathways. Rac3 is a member of the Rac subfamily of the Rho family of small G proteins.[6][7] Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.[5]
Interactions
RAC3 has been shown to interact with CIB1[8] and HNF1A.[9] RAC3 also interacts with Nrf2 proteins.[10] ETAR, ILK, and β-arr1 interact with RAC3 as well.[11]
Location
RAC3 gene is located in the third sub-band of the fifth band in the second region of the q arm on chromosome 17. There's many tumor suppressor genes that are located around the RAC3 gene.[12]
Therapeutic Use
Since the RAC3 gene is over-expressed in carcinoma cells, it can function as a therapeutic target for the treatment of different cancer such as lung adenocarcinoma. To become invasive, epithelial cells have to transform into mesenchymal cells and the transformation is regulated by the RAC3 gene. As a result, if the RAC3 gene is silenced, lung adenocarcinoma cells cannot metastasize. In addition, drugs designed to silence the RAC3 gene lead to the apoptosis of tumor cells, thus preventing the cells from colonizing.[13]
Pathological mutations
Mutations of the RAC3 gene may result in neurodevelopmental disorder with structural brain anomalies and dysmorphic facies, first described in 2018 by White et al.
References
- GRCh38: Ensembl release 89: ENSG00000169750 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000018012 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Entrez Gene: RAC3 ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3)".
- Courjal F, Chuchana P, Theillet C, Fort P (September 1997). "Structure and chromosomal assignment to 22q12 and 17qter of the ras-related Rac2 and Rac3 human genes". Genomics. 44 (2): 242–6. doi:10.1006/geno.1997.4871. PMID 9299243.
- Haataja L, Groffen J, Heisterkamp N (August 1997). "Characterization of RAC3, a novel member of the Rho family". The Journal of Biological Chemistry. 272 (33): 20384–8. doi:10.1074/jbc.272.33.20384. PMID 9252344.
- Haataja L, Kaartinen V, Groffen J, Heisterkamp N (March 2002). "The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading". The Journal of Biological Chemistry. 277 (10): 8321–8. doi:10.1074/jbc.M105363200. PMID 11756406.
yes
- Soutoglou E, Papafotiou G, Katrakili N, Talianidis I (April 2000). "Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins". The Journal of Biological Chemistry. 275 (17): 12515–20. doi:10.1074/jbc.275.17.12515. PMID 10777539.
yes
- Kim JH, Yu S, Chen JD, Kong AN (January 2013). "The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains". Oncogene. 32 (4): 514–27. doi:10.1038/onc.2012.59. PMC 3538952. PMID 22370642.
- Masi I, Caprara V, Spadaro F, Chellini L, Sestito R, Zancla A, et al. (March 2021). "Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK". Cell Reports. 34 (9): 108800. doi:10.1016/j.celrep.2021.108800. PMID 33657382.
- Morris CM, Haataja L, McDonald M, Gough S, Markie D, Groffen J, Heisterkamp N (2000). "The small GTPase RAC3 gene is located within chromosome band 17q25.3 outside and telomeric of a region commonly deleted in breast and ovarian tumours". Cytogenetics and Cell Genetics. 89 (1–2): 18–23. doi:10.1159/000015583. PMID 10894930. S2CID 22901214.
- de Curtis I (September 2019). "The Rac3 GTPase in Neuronal Development, Neurodevelopmental Disorders, and Cancer". Cells. 8 (9): 1063. doi:10.3390/cells8091063. PMC 6770886. PMID 31514269.
Further reading
- Didsbury J, Weber RF, Bokoch GM, Evans T, Snyderman R (October 1989). "rac, a novel ras-related family of proteins that are botulinum toxin substrates". The Journal of Biological Chemistry. 264 (28): 16378–82. doi:10.1016/S0021-9258(19)84716-6. PMID 2674130.
- Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Haataja L, Groffen J, Heisterkamp N (August 1997). "Characterization of RAC3, a novel member of the Rho family". The Journal of Biological Chemistry. 272 (33): 20384–8. doi:10.1074/jbc.272.33.20384. PMID 9252344.
- Courjal F, Chuchana P, Theillet C, Fort P (September 1997). "Structure and chromosomal assignment to 22q12 and 17qter of the ras-related Rac2 and Rac3 human genes". Genomics. 44 (2): 242–6. doi:10.1006/geno.1997.4871. PMID 9299243.
- Mira JP, Benard V, Groffen J, Sanders LC, Knaus UG (January 2000). "Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway". Proceedings of the National Academy of Sciences of the United States of America. 97 (1): 185–9. Bibcode:2000PNAS...97..185M. doi:10.1073/pnas.97.1.185. PMC 26637. PMID 10618392.
- Soutoglou E, Papafotiou G, Katrakili N, Talianidis I (April 2000). "Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins". The Journal of Biological Chemistry. 275 (17): 12515–20. doi:10.1074/jbc.275.17.12515. PMID 10777539.
- Morris CM, Haataja L, McDonald M, Gough S, Markie D, Groffen J, Heisterkamp N (2000). "The small GTPase RAC3 gene is located within chromosome band 17q25.3 outside and telomeric of a region commonly deleted in breast and ovarian tumours". Cytogenetics and Cell Genetics. 89 (1–2): 18–23. doi:10.1159/000015583. PMID 10894930. S2CID 22901214.
- Gnanapragasam VJ, Leung HY, Pulimood AS, Neal DE, Robson CN (December 2001). "Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer". British Journal of Cancer. 85 (12): 1928–36. doi:10.1054/bjoc.2001.2179. PMC 2364015. PMID 11747336.
- Haataja L, Kaartinen V, Groffen J, Heisterkamp N (March 2002). "The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading". The Journal of Biological Chemistry. 277 (10): 8321–8. doi:10.1074/jbc.M105363200. PMID 11756406.
- De Langhe S, Haataja L, Senadheera D, Groffen J, Heisterkamp N (May 2002). "Interaction of the small GTPase Rac3 with NRBP, a protein with a kinase-homology domain". International Journal of Molecular Medicine. 9 (5): 451–9. doi:10.3892/ijmm.9.5.451. PMID 11956649.
- Zhang A, Yeung PL, Li CW, Tsai SC, Dinh GK, Wu X, et al. (August 2004). "Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators". The Journal of Biological Chemistry. 279 (32): 33799–805. doi:10.1074/jbc.M403997200. PMID 15184363.
- Hwang SL, Chang JH, Cheng TS, Sy WD, Lieu AS, Lin CL, et al. (June 2005). "Expression of Rac3 in human brain tumors". Journal of Clinical Neuroscience. 12 (5): 571–4. doi:10.1016/j.jocn.2004.08.013. PMID 15993075. S2CID 24196818.
- Chan AY, Coniglio SJ, Chuang YY, Michaelson D, Knaus UG, Philips MR, Symons M (November 2005). "Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion". Oncogene. 24 (53): 7821–9. doi:10.1038/sj.onc.1208909. PMID 16027728.
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
- Baugher PJ, Krishnamoorthy L, Price JE, Dharmawardhane SF (2006). "Rac1 and Rac3 isoform activation is involved in the invasive and metastatic phenotype of human breast cancer cells". Breast Cancer Research. 7 (6): R965-74. doi:10.1186/bcr1329. PMC 1410764. PMID 16280046.
- Watabe-Uchida M, John KA, Janas JA, Newey SE, Van Aelst L (September 2006). "The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18". Neuron. 51 (6): 727–39. doi:10.1016/j.neuron.2006.07.020. PMID 16982419. S2CID 14871329.
- Hajdo-Milasinović A, Ellenbroek SI, van Es S, van der Vaart B, Collard JG (February 2007). "Rac1 and Rac3 have opposing functions in cell adhesion and differentiation of neuronal cells". Journal of Cell Science. 120 (Pt 4): 555–66. doi:10.1242/jcs.03364. PMID 17244648.
External links
- RAC3 Info with links in the Cell Migration Gateway Archived 2014-12-11 at the Wayback Machine
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