RASSF5 explained

Ras association domain-containing protein 5 is a protein that in humans is encoded by the RASSF5 or F5 gene.^{[1] [2] [3]}

Function

This gene is a member of the Ras association domain family. It functions as a tumor suppressor, and is inactivated in a variety of cancers. The encoded protein localizes to centrosomes and microtubules, and associates with the GTP-activated forms of Ras, Rap1, and several other Ras-like small GTPases. The protein regulates lymphocyte adhesion and suppresses cell growth in response to activated Rap1 or Ras. Multiple transcript variants encoding different isoforms have been found for this gene.

Interactions

RASSF5 has been shown to interact with RRAS,^[4] RAP2A,^[4] MRAS^[4] and RASSF1.^[4]

Further reading

• Kumari G, Singhal PK, Suryaraja R, Mahalingam S . Functional interaction of the Ras effector RASSF5 with the tyrosine kinase Lck: critical role in nucleocytoplasmic transport and cell cycle regulation . Journal of Molecular Biology . 397 . 1 . 89–109 . Mar 2010 . 20064523 . 10.1016/j.jmb.2010.01.005 .
• Vavvas D, Li X, Avruch J, Zhang XF . Identification of Nore1 as a potential Ras effector . The Journal of Biological Chemistry . 273 . 10 . 5439–42 . Mar 1998 . 9488663 . 10.1074/jbc.273.10.5439 . free .
• Ortiz-Vega S, Khokhlatchev A, Nedwidek M, Zhang XF, Dammann R, Pfeifer GP, Avruch J . The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1 . Oncogene . 21 . 9 . 1381–90 . Feb 2002 . 11857081 . 10.1038/sj.onc.1205192 . free .
• Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J . Identification of a novel Ras-regulated proapoptotic pathway . Current Biology . 12 . 4 . 253–65 . Feb 2002 . 11864565 . 10.1016/S0960-9822(02)00683-8 . 14053233 . free . 2002CBio...12..253K .
• Vos MD, Martinez A, Ellis CA, Vallecorsa T, Clark GJ . The pro-apoptotic Ras effector Nore1 may serve as a Ras-regulated tumor suppressor in the lung . The Journal of Biological Chemistry . 278 . 24 . 21938–43 . Jun 2003 . 12676952 . 10.1074/jbc.M211019200 . free .
• Katagiri K, Maeda A, Shimonaka M, Kinashi T . RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1 . Nature Immunology . 4 . 8 . 741–8 . Aug 2003 . 12845325 . 10.1038/ni950 . 10588415 .
• Chen J, Lui WO, Vos MD, Clark GJ, Takahashi M, Schoumans J, Khoo SK, Petillo D, Lavery T, Sugimura J, Astuti D, Zhang C, Kagawa S, Maher ER, Larsson C, Alberts AS, Kanayama HO, Teh BT . The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell renal cell carcinomas . Cancer Cell . 4 . 5 . 405–13 . Nov 2003 . 14667507 . 10.1016/S1535-6108(03)00269-1 . free .
• Praskova M, Khoklatchev A, Ortiz-Vega S, Avruch J . Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras . The Biochemical Journal . 381 . Pt 2 . 453–62 . Jul 2004 . 15109305 . 1133852 . 10.1042/BJ20040025 .
• Irimia M, Fraga MF, Sanchez-Cespedes M, Esteller M . CpG island promoter hypermethylation of the Ras-effector gene NORE1A occurs in the context of a wild-type K-ras in lung cancer . Oncogene . 23 . 53 . 8695–9 . Nov 2004 . 15378027 . 10.1038/sj.onc.1207914 . free .
• Fujita H, Fukuhara S, Sakurai A, Yamagishi A, Kamioka Y, Nakaoka Y, Masuda M, Mochizuki N . Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes . The Journal of Biological Chemistry . 280 . 6 . 5022–31 . Feb 2005 . 15569673 . 10.1074/jbc.M409701200 . free .
• Nakamura N, Carney JA, Jin L, Kajita S, Pallares J, Zhang H, Qian X, Sebo TJ, Erickson LA, Lloyd RV . RASSF1A and NORE1A methylation and BRAFV600E mutations in thyroid tumors . Laboratory Investigation . 85 . 9 . 1065–75 . Sep 2005 . 15980887 . 10.1038/labinvest.3700306 . free .
• Foukakis T, Au AY, Wallin G, Geli J, Forsberg L, Clifton-Bligh R, Robinson BG, Lui WO, Zedenius J, Larsson C . The Ras effector NORE1A is suppressed in follicular thyroid carcinomas with a PAX8-PPARgamma fusion . The Journal of Clinical Endocrinology and Metabolism . 91 . 3 . 1143–9 . Mar 2006 . 16352687 . 10.1210/jc.2005-1372 . free .
• Moshnikova A, Frye J, Shay JW, Minna JD, Khokhlatchev AV . The growth and tumor suppressor NORE1A is a cytoskeletal protein that suppresses growth by inhibition of the ERK pathway . The Journal of Biological Chemistry . 281 . 12 . 8143–52 . Mar 2006 . 16421102 . 10.1074/jbc.M511837200 . free .
• Macheiner D, Heller G, Kappel S, Bichler C, Stättner S, Ziegler B, Kandioler D, Wrba F, Schulte-Hermann R, Zöchbauer-Müller S, Grasl-Kraupp B . NORE1B, a candidate tumor suppressor, is epigenetically silenced in human hepatocellular carcinoma . Journal of Hepatology . 45 . 1 . 81–9 . Jul 2006 . 16516329 . 10.1016/j.jhep.2005.12.017 .
• Ishiguro K, Avruch J, Landry A, Qin S, Ando T, Goto H, Xavier R . Nore1B regulates TCR signaling via Ras and Carma1 . Cellular Signalling . 18 . 10 . 1647–54 . Oct 2006 . 16520020 . 3204664 . 10.1016/j.cellsig.2006.01.015 .

Notes and References

1. Yao R, Wang Y, You M . Chromosome mapping and sequence variation of the murine Ras effector gene Nore1 . Cytogenetics and Cell Genetics . 95 . 1–2 . 126–8 . Apr 2002 . 11978988 . 10.1159/000057035 . 26933977 .
2. Tommasi S, Dammann R, Jin SG, Zhang XF, Avruch J, Pfeifer GP . RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1 . Oncogene . 21 . 17 . 2713–20 . Apr 2002 . 11965544 . 10.1038/sj.onc.1205365 . free .
3. Web site: Entrez Gene: RASSF5 Ras association (RalGDS/AF-6) domain family 5.
4. Ortiz-Vega S, Khokhlatchev A, Nedwidek M, Zhang XF, Dammann R, Pfeifer GP, Avruch J . The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1 . Oncogene . 21 . 9 . 1381–90 . Feb 2002 . 11857081 . 10.1038/sj.onc.1205192 . free .