RAC1

出典: フリー百科事典『ウィキペディア(Wikipedia)』
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Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)

PDB rendering based on 1ds6.
Available structures
PDB Ortholog search: PDBe, RCSB
識別記号
記号英語版 RAC1; Rac-1; TC-25; p21-Rac1
その他ID OMIM英語版602048 MGI英語版97845 HomoloGene英語版69035 ChEMBL: 6094 GeneCards: RAC1 Gene
RNA発現パターン
PBB GE RAC1 208640 at tn.png
PBB GE RAC1 208641 s at tn.png
その他参照発現データ
オルソログ
ヒト マウス
Entrez英語版 5879 19353
Ensembl英語版 ENSG00000136238 ENSMUSG00000001847
UniProt英語版 P63000 P63001
RefSeq (mRNA) NM_006908 NM_009007
RefSeq (protein) NP_008839 NP_033033
Location (UCSC) Chr 7:
6.41 - 6.44 Mb
Chr 5:
143.51 - 143.53 Mb
PubMed search [1] [2]

Rac1(RAS-related C3 botulinus toxin substrate 1) は、ヒト細胞に存在するタンパク質であり、RAC1遺伝子によりコードされている[1][2]RAC1選択的スプライシングにより異なる機能を持ったいくつかのタンパク質を生成し、このうちのひとつがRac1である[3]

Rac1は、悪性黒色腫[4][5][6]肺非小細胞癌[7] を含む様々なの発生おいて重要な役割を果たしていると考えられている。

そのため現在、これらの疾患に対する治療標的と考えられている[8]

機能[編集]

Rac1は、低分子量GTPアーゼのひとつであり、さらに、RhoファミリーGタンパク質であるRacサブファミリーのメンバーである。このスーパーファミリーのメンバーは、細胞の増殖細胞骨格の再構築、プロテインキナーゼの活性化など様々な細胞における事象を制御している[9]

Rac1は、細胞周期細胞接着、(アクチンネットワークを介した)細胞運動、上皮細胞における悪性形質転換上皮幹細胞維持における必要物質であると考えられている)などを含む多くの細胞プロセスにおける多方面的な制御因子である。

相互作用[編集]

ARFIP2[10][11][12]Myotonic dystrophy protein kinase[13]T-cell lymphoma invasion and metastasis-inducing protein 1[14][15]PARD6B[16]PAK1[17][18][19]PAK3[10]ARHGDIA[20][21][22][23][24][25]Myd88[26]PARD6A,[16][27]STAT3[28]IQGAP2[29]NCKAP1[30]IQGAP1[19][31][32][33]FHOD1[34]BAIAP2[35]RICS[36][37]FMNL1[38] などのタンパク質と相互作用することが明らかにされている。

脚注[編集]

  1. ^ 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”. J. Biol. Chem. 264 (28): 16378–82. PMID 2674130. 
  2. ^ Jordan P, Brazåo R, Boavida MG, Gespach C, Chastre E (November 1999). “Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors”. Oncogene 18 (48): 6835–9. doi:10.1038/sj.onc.1203233. PMID 10597294. 
  3. ^ Zhou, C; Licciulli, S; Avila, J L; Cho, M; Troutman, S; Jiang, P; Kossenkov, A V; Showe, L C et al. (2012). “The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis”. Oncogene. doi:10.1038/onc.2012.99. ISSN 0950-9232. 
  4. ^ Hodis, E; Watson, IR; Kryukov, GV; Arold, ST; Imielinski, M; Theurillat, JP; Nickerson, E; Auclair, D; Li, L; Place, C; Dicara, D; Ramos, AH; Lawrence, MS; Cibulskis, K; Sivachenko, A; Voet, D; Saksena, G; Stransky, N; Onofrio, RC; Winckler, W; Ardlie, K; Wagle, N; Wargo, J; Chong, K; Morton, DL; Stemke-Hale, K; Chen, G; Noble, M; Meyerson, M; Ladbury, JE; Davies, MA; Gershenwald, JE; Wagner, SN; Hoon, DS; Schadendorf, D; Lander, ES; Gabriel, SB; Getz, G; Garraway, LA; Chin, L (2012 Jul 18). “A landscape of driver mutations in melanoma.”. Cell. PMID 22817889. 
  5. ^ Krauthammer, M; Kong, Y; Ha, BH; Evans, P; Bacchiocchi, A; McCusker, JP; Cheng, E; Davis, MJ; Goh, G; Choi, M; Ariyan, S; Narayan, D; Dutton-Regester, K; Capatana, A; Holman, EC; Bosenberg, M; Sznol, M; Kluger, HM; Brash, DE; Stern, DF; Materin, MA; Lo, RS; Mane, S; Ma, S; Kidd, KK; Hayward, NK; Lifton, RP; Schlessinger, J; Boggon, TJ; Halaban, R (2012 Jul 29). “Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma.”. Nature genetics. PMID 22842228. 
  6. ^ Bauer, Natalie N.; Chen, Yih-Wen; Samant, Rajeev S.; Shevde, Lalita A.; Fodstad, Oystein (2007). “Rac1 activity regulates proliferation of aggressive metastatic melanoma”. Experimental Cell Research 313 (18): 3832–3839. doi:10.1016/j.yexcr.2007.08.017. ISSN 00144827. 
  7. ^ Stallings-Mann, M. L.; Waldmann, J.; Zhang, Y.; Miller, E.; Gauthier, M. L.; Visscher, D. W.; Downey, G. P.; Radisky, E. S. et al. (2012). “Matrix Metalloproteinase Induction of Rac1b, a Key Effector of Lung Cancer Progression”. Science Translational Medicine 4 (142): 142ra95–142ra95. doi:10.1126/scitranslmed.3004062. ISSN 1946-6234. 
  8. ^ McAllister, S. S. (2012). “Got a Light? Illuminating Lung Cancer”. Science Translational Medicine 4 (142): 142fs22–142fs22. doi:10.1126/scitranslmed.3004446. ISSN 1946-6234. 
  9. ^ Ridley A. (2006). “Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking”. Trends Cell Biol 16 (10): 522–9. doi:10.1016/j.tcb.2006.08.006. ISSN 0962-8924. PMID 16949823. 
  10. ^ a b Shin, O H; Exton J H (August 2001). “Differential binding of arfaptin 2/POR1 to ADP-ribosylation factors and Rac1”. Biochem. Biophys. Res. Commun. (United States) 285 (5): 1267–73. doi:10.1006/bbrc.2001.5330. ISSN 0006-291X. PMID 11478794. 
  11. ^ Van Aelst, L; Joneson T, Bar-Sagi D (August 1996). “Identification of a novel Rac1-interacting protein involved in membrane ruffling”. EMBO J. (ENGLAND) 15 (15): 3778–86. ISSN 0261-4189. PMC 452058. PMID 8670882. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=452058. 
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  13. ^ Shimizu, M; Wang W, Walch E T, Dunne P W, Epstein H F (June 2000). “Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase”. FEBS Lett. (NETHERLANDS) 475 (3): 273–7. doi:10.1016/S0014-5793(00)01692-6. ISSN 0014-5793. PMID 10869570. 
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  16. ^ a b Noda, Y; Takeya R, Ohno S, Naito S, Ito T, Sumimoto H (February 2001). “Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C”. Genes Cells (England) 6 (2): 107–19. doi:10.1046/j.1365-2443.2001.00404.x. ISSN 1356-9597. PMID 11260256. 
  17. ^ Katoh, Hironori; Negishi Manabu (July 2003). “RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo”. Nature (England) 424 (6947): 461–4. doi:10.1038/nature01817. PMID 12879077. 
  18. ^ Seoh, Mui Leng; Ng Chong Han, Yong Jeffery, Lim Louis, Leung Thomas (March 2003). “ArhGAP15, a novel human RacGAP protein with GTPase binding property”. FEBS Lett. (Netherlands) 539 (1–3): 131–7. doi:10.1016/S0014-5793(03)00213-8. ISSN 0014-5793. PMID 12650940. 
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  20. ^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). “Large-scale mapping of human protein–protein interactions by mass spectrometry”. Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948. 
  21. ^ Grizot, S; Fauré J, Fieschi F, Vignais P V, Dagher M C, Pebay-Peyroula E (August 2001). “Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation”. Biochemistry (United States) 40 (34): 10007–13. doi:10.1021/bi010288k. ISSN 0006-2960. PMID 11513578. 
  22. ^ Lian, L Y; Barsukov I, Golovanov A P, Hawkins D I, Badii R, Sze K H, Keep N H, Bokoch G M, Roberts G C (January 2000). “Mapping the binding site for the GTP-binding protein Rac-1 on its inhibitor RhoGDI-1”. Structure (ENGLAND) 8 (1): 47–55. doi:10.1016/S0969-2126(00)00080-0. ISSN 0969-2126. PMID 10673424. 
  23. ^ Gorvel, J P; Chang T C, Boretto J, Azuma T, Chavrier P (January 1998). “Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity”. FEBS Lett. (NETHERLANDS) 422 (2): 269–73. doi:10.1016/S0014-5793(98)00020-9. ISSN 0014-5793. PMID 9490022. 
  24. ^ Di-Poï, N; Fauré J, Grizot S, Molnár G, Pick E, Dagher M C (August 2001). “Mechanism of NADPH oxidase activation by the Rac/Rho-GDI complex”. Biochemistry (United States) 40 (34): 10014–22. doi:10.1021/bi010289c. ISSN 0006-2960. PMID 11513579. 
  25. ^ Fauré, J; Dagher M C (May 2001). “Interactions between Rho GTPases and Rho GDP dissociation inhibitor (Rho-GDI)”. Biochimie (France) 83 (5): 409–14. doi:10.1016/S0300-9084(01)01263-9. ISSN 0300-9084. PMID 11368848. 
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  27. ^ Qiu, R G; Abo A, Steven Martin G (June 2000). “A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation”. Curr. Biol. (ENGLAND) 10 (12): 697–707. doi:10.1016/S0960-9822(00)00535-2. ISSN 0960-9822. PMID 10873802. 
  28. ^ Simon, A R; Vikis H G, Stewart S, Fanburg B L, Cochran B H, Guan K L (October 2000). “Regulation of STAT3 by direct binding to the Rac1 GTPase”. Science (UNITED STATES) 290 (5489): 144–7. doi:10.1126/science.290.5489.144. ISSN 0036-8075. PMID 11021801. 
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  31. ^ Kuroda, S; Fukata M, Kobayashi K, Nakafuku M, Nomura N, Iwamatsu A, Kaibuchi K (September 1996). “Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1”. J. Biol. Chem. (UNITED STATES) 271 (38): 23363–7. doi:10.1074/jbc.271.38.23363. ISSN 0021-9258. PMID 8798539. 
  32. ^ Fukata, Masaki; Watanabe Takashi, Noritake Jun, Nakagawa Masato, Yamaga Masaki, Kuroda Shinya, Matsuura Yoshiharu, Iwamatsu Akihiro, Perez Franck, Kaibuchi Kozo (June 2002). “Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170”. Cell (United States) 109 (7): 873–85. doi:10.1016/S0092-8674(02)00800-0. ISSN 0092-8674. PMID 12110184. 
  33. ^ Hart, M J; Callow M G, Souza B, Polakis P (June 1996). “IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs”. EMBO J. (ENGLAND) 15 (12): 2997–3005. ISSN 0261-4189. PMC 450241. PMID 8670801. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=450241. 
  34. ^ Westendorf, J J (Dec. 2001). “The formin/diaphanous-related protein, FHOS, interacts with Rac1 and activates transcription from the serum response element”. J. Biol. Chem. (United States) 276 (49): 46453–9. doi:10.1074/jbc.M105162200. ISSN 0021-9258. PMID 11590143. 
  35. ^ Miki, H; Yamaguchi H, Suetsugu S, Takenawa T (Dec. 2000). “IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling”. Nature (England) 408 (6813): 732–5. doi:10.1038/35047107. ISSN 0028-0836. PMID 11130076. 
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推薦文献[編集]

  • Benitah SA, Frye M, Glogauer M, Watt FM (2005). “Stem cell depletion through epidermal deletion of Rac1”. Science 309 (5736): 933–5. doi:10.1126/science.1113579. PMID 16081735. 
  • Dorseuil O, Gacon G (1997). “[Signal transduction by Rac small G proteins in phagocytes] [Signal transduction by Rac small G proteins in phagocytes]” (French). C. R. Seances Soc. Biol. Fil. 191 (2): 237–46. PMID 9255350. 
  • Ramakers GJ (2002). “Rho proteins, mental retardation and the cellular basis of cognition”. Trends Neurosci. 25 (4): 191–9. doi:10.1016/S0166-2236(00)02118-4. PMID 11998687. 
  • Esufali S, Charames S, Bapat B (2007). “Suppression of Wnt signalling leads to stabilization of Rac1 isoforms”. FEBS letters. 581 (25): 4850–4856. doi:10.1016/j.febslet.2007.09.013. PMID 17888911. 

外部リンク[編集]