RAC3 explained

Ras-related C3 botulinum toxin substrate 3 (Rac3) is a G protein that in humans is encoded by the RAC3 gene.^[1] 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.^{[2] [3]} 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.^[1]

Interactions

RAC3 has been shown to interact with CIB1^[4] and HNF1A.^[5] RAC3 also interacts with Nrf2 proteins.^[6] ET_AR, ILK, and β-arr1 interact with RAC3 as well.^[7]

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.^[8]

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.^[9]

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.

Further reading

• Didsbury J, Weber RF, Bokoch GM, Evans T, Snyderman R . rac, a novel ras-related family of proteins that are botulinum toxin substrates . The Journal of Biological Chemistry . 264 . 28 . 16378–82 . October 1989 . 10.1016/S0021-9258(19)84716-6 . 2674130 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Haataja L, Groffen J, Heisterkamp N . Characterization of RAC3, a novel member of the Rho family . The Journal of Biological Chemistry . 272 . 33 . 20384–8 . August 1997 . 9252344 . 10.1074/jbc.272.33.20384 . free .
• Courjal F, Chuchana P, Theillet C, Fort P . Structure and chromosomal assignment to 22q12 and 17qter of the ras-related Rac2 and Rac3 human genes . Genomics . 44 . 2 . 242–6 . September 1997 . 9299243 . 10.1006/geno.1997.4871 .
• Mira JP, Benard V, Groffen J, Sanders LC, Knaus UG . 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 . January 2000 . 10618392 . 26637 . 10.1073/pnas.97.1.185 . 2000PNAS...97..185M . free .
• Soutoglou E, Papafotiou G, Katrakili N, Talianidis I . Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins . The Journal of Biological Chemistry . 275 . 17 . 12515–20 . April 2000 . 10777539 . 10.1074/jbc.275.17.12515 . free .
• Morris CM, Haataja L, McDonald M, Gough S, Markie D, Groffen J, Heisterkamp N . 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 . 2000 . 10894930 . 10.1159/000015583 . 22901214 .
• Gnanapragasam VJ, Leung HY, Pulimood AS, Neal DE, Robson CN . Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer . British Journal of Cancer . 85 . 12 . 1928–36 . December 2001 . 11747336 . 2364015 . 10.1054/bjoc.2001.2179 .
• Haataja L, Kaartinen V, Groffen J, Heisterkamp N . 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 . March 2002 . 11756406 . 10.1074/jbc.M105363200 . free .
• De Langhe S, Haataja L, Senadheera D, Groffen J, Heisterkamp N . Interaction of the small GTPase Rac3 with NRBP, a protein with a kinase-homology domain . International Journal of Molecular Medicine . 9 . 5 . 451–9 . May 2002 . 11956649 . 10.3892/ijmm.9.5.451 .
• Zhang A, Yeung PL, Li CW, Tsai SC, Dinh GK, Wu X, Li H, Chen JD . 6 . Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators . The Journal of Biological Chemistry . 279 . 32 . 33799–805 . August 2004 . 15184363 . 10.1074/jbc.M403997200 . free .
• Hwang SL, Chang JH, Cheng TS, Sy WD, Lieu AS, Lin CL, Lee KS, Howng SL, Hong YR . 6 . Expression of Rac3 in human brain tumors . Journal of Clinical Neuroscience . 12 . 5 . 571–4 . June 2005 . 15993075 . 10.1016/j.jocn.2004.08.013 . 24196818 .
• Chan AY, Coniglio SJ, Chuang YY, Michaelson D, Knaus UG, Philips MR, Symons M . Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion . Oncogene . 24 . 53 . 7821–9 . November 2005 . 16027728 . 10.1038/sj.onc.1208909 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 4427026 . 2005Natur.437.1173R .
• Baugher PJ, Krishnamoorthy L, Price JE, Dharmawardhane SF . 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 . 2006 . 16280046 . 1410764 . 10.1186/bcr1329 . free .
• Watabe-Uchida M, John KA, Janas JA, Newey SE, Van Aelst L . The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18 . Neuron . 51 . 6 . 727–39 . September 2006 . 16982419 . 10.1016/j.neuron.2006.07.020 . 14871329 . free .
• Hajdo-Milasinović A, Ellenbroek SI, van Es S, van der Vaart B, Collard JG . Rac1 and Rac3 have opposing functions in cell adhesion and differentiation of neuronal cells . Journal of Cell Science . 120 . Pt 4 . 555–66 . February 2007 . 17244648 . 10.1242/jcs.03364 . free .

External links

• RAC3 Info with links in the Cell Migration Gateway

Notes and References

1. Web site: Entrez Gene: RAC3 ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3).
2. Courjal F, Chuchana P, Theillet C, Fort P . Structure and chromosomal assignment to 22q12 and 17qter of the ras-related Rac2 and Rac3 human genes . Genomics . 44 . 2 . 242–6 . September 1997 . 9299243 . 10.1006/geno.1997.4871 .
3. Haataja L, Groffen J, Heisterkamp N . Characterization of RAC3, a novel member of the Rho family . The Journal of Biological Chemistry . 272 . 33 . 20384–8 . August 1997 . 9252344 . 10.1074/jbc.272.33.20384 . free .
4. Haataja L, Kaartinen V, Groffen J, Heisterkamp N . 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 . March 2002 . 11756406 . 10.1074/jbc.M105363200 . yes . free .
5. Soutoglou E, Papafotiou G, Katrakili N, Talianidis I . Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins . The Journal of Biological Chemistry . 275 . 17 . 12515–20 . April 2000 . 10777539 . 10.1074/jbc.275.17.12515 . yes . free .
6. Kim JH, Yu S, Chen JD, Kong AN . The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains . Oncogene . 32 . 4 . 514–27 . January 2013 . 22370642 . 3538952 . 10.1038/onc.2012.59 .
7. Masi I, Caprara V, Spadaro F, Chellini L, Sestito R, Zancla A, Rainer A, Bagnato A, Rosanò L . 6 . Endothelin-1 drives invadopodia and interaction with mesothelial cells through ILK . Cell Reports . 34 . 9 . 108800 . March 2021 . 33657382 . 10.1016/j.celrep.2021.108800 . free .
8. Morris CM, Haataja L, McDonald M, Gough S, Markie D, Groffen J, Heisterkamp N . 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 . 2000 . 10894930 . 10.1159/000015583 . 22901214 .
9. de Curtis I . The Rac3 GTPase in Neuronal Development, Neurodevelopmental Disorders, and Cancer . Cells . 8 . 9 . September 2019 . 1063 . 31514269 . 6770886 . 10.3390/cells8091063 . free .