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Gene Review

RASSF1  -  Ras association (RalGDS/AF-6) domain...

Homo sapiens

Synonyms: 123F2, NORE2A, RASSF1A, RDA32, REH3P21, ...
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Disease relevance of RASSF1


High impact information on RASSF1


Chemical compound and disease context of RASSF1


Biological context of RASSF1

  • We explored the hypothesis that RASSF1 encodes a tumor suppressor gene for lung and breast cancers [16].
  • BACKGROUND: The recently identified RASSF1 locus is located within a 120-kilobase region of chromosome 3p21.3 that frequently undergoes allele loss in lung and breast cancers [16].
  • The activities of RASSF2, which were distinct from those of RASSF1, included induction of morphologic changes and apoptosis; moreover, its ability to prevent cell transformation suggests that RASSF2 acts as a tumor suppressor in CRC [12].
  • In this study, we investigated the expression and methylation status of the RASSF1 gene in thyroid carcinoma [17].
  • Recently, two related novel Ras effectors, NORE1 and RASSF1, have been identified as mediators of apoptosis and cell cycle arrest [18].

Anatomical context of RASSF1


Associations of RASSF1 with chemical compounds


Physical interactions of RASSF1

  • The scaffold protein CNK1 interacts with the tumor suppressor RASSF1A and augments RASSF1A-induced cell death [26].
  • We now identify a novel pathway connecting RASSF1A to Bax via the Bax binding protein MOAP-1 [27].
  • Conversely depletion of RABP1 by RNA interference prevented both the localization of RASSF1A to the spindle poles as well as its binding to Cdc20, resulting in premature destruction of mitotic cyclins and acceleration of mitotic progression [28].
  • The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1 [29].
  • These results provide evidence for the first time that arginine-rich signals are able to recognize different nuclear import receptors and transport the RASSF proteins into distinct sub-cellular compartments [30].
  • We show that key steps in RASSF1A-induced apoptosis are the disruption of the inhibitory Raf1-MST2 complex by RASSF1A and the concomitant enhancement of MST2 interaction with its substrate, LATS1 [31].

Regulatory relationships of RASSF1


Other interactions of RASSF1


Analytical, diagnostic and therapeutic context of RASSF1


  1. RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1. Tommasi, S., Dammann, R., Jin, S.G., Zhang Xf, X.F., Avruch, J., Pfeifer, G.P. Oncogene (2002) [Pubmed]
  2. Implications of methylation patterns of cancer genes in salivary gland tumors. Williams, M.D., Chakravarti, N., Kies, M.S., Maruya, S., Myers, J.N., Haviland, J.C., Weber, R.S., Lotan, R., El-Naggar, A.K. Clin. Cancer Res. (2006) [Pubmed]
  3. RASSF1A gene inactivation in non-small cell lung cancer and its clinical implication. Endoh, H., Yatabe, Y., Shimizu, S., Tajima, K., Kuwano, H., Takahashi, T., Mitsudomi, T. Int. J. Cancer (2003) [Pubmed]
  4. Inactivation of the RASSF1A in osteosarcoma. Lim, S., Yang, M.H., Park, J.H., Nojima, T., Hashimoto, H., Unni, K.K., Park, Y.K. Oncol. Rep. (2003) [Pubmed]
  5. Epigenetic modifications of RASSF1A gene through chromatin remodeling in prostate cancer. Kawamoto, K., Okino, S.T., Place, R.F., Urakami, S., Hirata, H., Kikuno, N., Kawakami, T., Tanaka, Y., Pookot, D., Chen, Z., Majid, S., Enokida, H., Nakagawa, M., Dahiya, R. Clin. Cancer Res. (2007) [Pubmed]
  6. Latent membrane protein 1 suppresses RASSF1A expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells. Man, C., Rosa, J., Lee, L.T., Lee, V.H., Chow, B.K., Lo, K.W., Doxsey, S., Wu, Z.G., Kwong, Y.L., Jin, D.Y., Cheung, A.L., Tsao, S.W. Oncogene (2007) [Pubmed]
  7. RASSF1A, the new guardian of mitosis. Máthé, E. Nat. Genet. (2004) [Pubmed]
  8. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Dammann, R., Li, C., Yoon, J.H., Chin, P.L., Bates, S., Pfeifer, G.P. Nat. Genet. (2000) [Pubmed]
  9. Linking tumor suppression, DNA damage and the anaphase-promoting complex. Jackson, P.K. Trends Cell Biol. (2004) [Pubmed]
  10. The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death. Baksh, S., Tommasi, S., Fenton, S., Yu, V.C., Martins, L.M., Pfeifer, G.P., Latif, F., Downward, J., Neel, B.G. Mol. Cell (2005) [Pubmed]
  11. Multiplicity of abnormal promoter methylation in lung adenocarcinomas from smokers and never smokers. Divine, K.K., Pulling, L.C., Marron-Terada, P.G., Liechty, K.C., Kang, T., Schwartz, A.G., Bocklage, T.J., Coons, T.A., Gilliland, F.D., Belinsky, S.A. Int. J. Cancer (2005) [Pubmed]
  12. The Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancer. Akino, K., Toyota, M., Suzuki, H., Mita, H., Sasaki, Y., Ohe-Toyota, M., Issa, J.P., Hinoda, Y., Imai, K., Tokino, T. Gastroenterology (2005) [Pubmed]
  13. Epigenetic repression of RASSF1A but not CASP8 in supratentorial PNET (sPNET) and atypical teratoid/rhabdoid tumors (AT/RT) of childhood. Mühlisch, J., Schwering, A., Grotzer, M., Vince, G.H., Roggendorf, W., Hagemann, C., Sörensen, N., Rickert, C.H., Osada, N., Jürgens, H., Frühwald, M.C. Oncogene (2006) [Pubmed]
  14. RASSF1A promoter region CpG island hypermethylation in phaeochromocytomas and neuroblastoma tumours. Astuti, D., Agathanggelou, A., Honorio, S., Dallol, A., Martinsson, T., Kogner, P., Cummins, C., Neumann, H.P., Voutilainen, R., Dahia, P., Eng, C., Maher, E.R., Latif, F. Oncogene (2001) [Pubmed]
  15. Chronic oral exposure to inorganic arsenate interferes with methylation status of p16INK4a and RASSF1A and induces lung cancer in A/J mice. Cui, X., Wakai, T., Shirai, Y., Hatakeyama, K., Hirano, S. Toxicol. Sci. (2006) [Pubmed]
  16. Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. Burbee, D.G., Forgacs, E., Zöchbauer-Müller, S., Shivakumar, L., Fong, K., Gao, B., Randle, D., Kondo, M., Virmani, A., Bader, S., Sekido, Y., Latif, F., Milchgrub, S., Toyooka, S., Gazdar, A.F., Lerman, M.I., Zabarovsky, E., White, M., Minna, J.D. J. Natl. Cancer Inst. (2001) [Pubmed]
  17. Frequent epigenetic silencing of the CpG island promoter of RASSF1A in thyroid carcinoma. Schagdarsurengin, U., Gimm, O., Hoang-Vu, C., Dralle, H., Pfeifer, G.P., Dammann, R. Cancer Res. (2002) [Pubmed]
  18. RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor. Vos, M.D., Ellis, C.A., Elam, C., Ulku, A.S., Taylor, B.J., Clark, G.J. J. Biol. Chem. (2003) [Pubmed]
  19. Novel functional interaction between the plasma membrane Ca2+ pump 4b and the proapoptotic tumor suppressor Ras-associated factor 1 (RASSF1). Armesilla, A.L., Williams, J.C., Buch, M.H., Pickard, A., Emerson, M., Cartwright, E.J., Oceandy, D., Vos, M.D., Gillies, S., Clark, G.J., Neyses, L. J. Biol. Chem. (2004) [Pubmed]
  20. Tumor cell-specific BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fluid from ovarian cancer patients. Ibanez de Caceres, I., Battagli, C., Esteller, M., Herman, J.G., Dulaimi, E., Edelson, M.I., Bergman, C., Ehya, H., Eisenberg, B.L., Cairns, P. Cancer Res. (2004) [Pubmed]
  21. The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. Dreijerink, K., Braga, E., Kuzmin, I., Geil, L., Duh, F.M., Angeloni, D., Zbar, B., Lerman, M.I., Stanbridge, E.J., Minna, J.D., Protopopov, A., Li, J., Kashuba, V., Klein, G., Zabarovsky, E.R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  22. Frequent alterations of Ras signaling pathway genes in sporadic malignant melanomas. Reifenberger, J., Knobbe, C.B., Sterzinger, A.A., Blaschke, B., Schulte, K.W., Ruzicka, T., Reifenberger, G. Int. J. Cancer (2004) [Pubmed]
  23. Control of microtubule stability by the RASSF1A tumor suppressor. Liu, L., Tommasi, S., Lee, D.H., Dammann, R., Pfeifer, G.P. Oncogene (2003) [Pubmed]
  24. Single nucleotide polymorphism at codon 133 of the RASSF1 gene is preferentially associated with human lung adenocarcinoma risk. Kanzaki, H., Hanafusa, H., Yamamoto, H., Yasuda, Y., Imai, K., Yano, M., Aoe, M., Shimizu, N., Nakachi, K., Ouchida, M., Shimizu, K. Cancer Lett. (2006) [Pubmed]
  25. Chromatin inactivation precedes de novo DNA methylation during the progressive epigenetic silencing of the RASSF1A promoter. Strunnikova, M., Schagdarsurengin, U., Kehlen, A., Garbe, J.C., Stampfer, M.R., Dammann, R. Mol. Cell. Biol. (2005) [Pubmed]
  26. The scaffold protein CNK1 interacts with the tumor suppressor RASSF1A and augments RASSF1A-induced cell death. Rabizadeh, S., Xavier, R.J., Ishiguro, K., Bernabeortiz, J., Lopez-Ilasaca, M., Khokhlatchev, A., Mollahan, P., Pfeifer, G.P., Avruch, J., Seed, B. J. Biol. Chem. (2004) [Pubmed]
  27. The RASSF1A tumor suppressor activates Bax via MOAP-1. Vos, M.D., Dallol, A., Eckfeld, K., Allen, N.P., Donninger, H., Hesson, L.B., Calvisi, D., Latif, F., Clark, G.J. J. Biol. Chem. (2006) [Pubmed]
  28. The centrosomal protein RAS association domain family protein 1A (RASSF1A)-binding protein 1 regulates mitotic progression by recruiting RASSF1A to spindle poles. Song, M.S., Chang, J.S., Song, S.J., Yang, T.H., Lee, H., Lim, D.S. J. Biol. Chem. (2005) [Pubmed]
  29. The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1. Ortiz-Vega, S., Khokhlatchev, A., Nedwidek, M., Zhang, X.F., Dammann, R., Pfeifer, G.P., Avruch, J. Oncogene (2002) [Pubmed]
  30. Nuclear Transport of Ras-associated Tumor Suppressor Proteins: Different Transport Receptor Binding Specificities for Arginine-rich Nuclear Targeting Signals. Kumari, G., Singhal, P.K., Rao, M.R., Mahalingam, S. J. Mol. Biol. (2007) [Pubmed]
  31. RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Matallanas, D., Romano, D., Yee, K., Meissl, K., Kucerova, L., Piazzolla, D., Baccarini, M., Vass, J.K., Kolch, W., O'neill, E. Mol. Cell (2007) [Pubmed]
  32. RASSF1A hypermethylation and its inverse correlation with BRAF and/or KRAS mutations in MSI-associated endometrial carcinoma. Kang, S., Lee, J.M., Jeon, E.S., Lee, S., Kim, H., Kim, H.S., Seo, S.S., Park, S.Y., Sidransky, D., Dong, S.M. Int. J. Cancer (2006) [Pubmed]
  33. The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex. Song, M.S., Song, S.J., Ayad, N.G., Chang, J.S., Lee, J.H., Hong, H.K., Lee, H., Choi, N., Kim, J., Kim, H., Kim, J.W., Choi, E.J., Kirschner, M.W., Lim, D.S. Nat. Cell Biol. (2004) [Pubmed]
  34. Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis. Xing, M., Cohen, Y., Mambo, E., Tallini, G., Udelsman, R., Ladenson, P.W., Sidransky, D. Cancer Res. (2004) [Pubmed]
  35. Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis. Oh, H.J., Lee, K.K., Song, S.J., Jin, M.S., Song, M.S., Lee, J.H., Im, C.R., Lee, J.O., Yonehara, S., Lim, D.S. Cancer Res. (2006) [Pubmed]
  36. RASSF4/AD037 is a potential ras effector/tumor suppressor of the RASSF family. Eckfeld, K., Hesson, L., Vos, M.D., Bieche, I., Latif, F., Clark, G.J. Cancer Res. (2004) [Pubmed]
  37. Identification of a novel Ras-regulated proapoptotic pathway. Khokhlatchev, A., Rabizadeh, S., Xavier, R., Nedwidek, M., Chen, T., Zhang, X.F., Seed, B., Avruch, J. Curr. Biol. (2002) [Pubmed]
  38. Multigene methylation analysis of Wilms' tumour and adult renal cell carcinoma. Morris, M.R., Hesson, L.B., Wagner, K.J., Morgan, N.V., Astuti, D., Lees, R.D., Cooper, W.N., Lee, J., Gentle, D., Macdonald, F., Kishida, T., Grundy, R., Yao, M., Latif, F., Maher, E.R. Oncogene (2003) [Pubmed]
  39. NORE1A, a homologue of RASSF1A tumour suppressor gene is inactivated in human cancers. Hesson, L., Dallol, A., Minna, J.D., Maher, E.R., Latif, F. Oncogene (2003) [Pubmed]
  40. Aberrant promoter methylation and silencing of the RASSF1A gene in pediatric tumors and cell lines. Harada, K., Toyooka, S., Maitra, A., Maruyama, R., Toyooka, K.O., Timmons, C.F., Tomlinson, G.E., Mastrangelo, D., Hay, R.J., Minna, J.D., Gazdar, A.F. Oncogene (2002) [Pubmed]
  41. Identification of novel gene expression targets for the Ras association domain family 1 (RASSF1A) tumor suppressor gene in non-small cell lung cancer and neuroblastoma. Agathanggelou, A., Bièche, I., Ahmed-Choudhury, J., Nicke, B., Dammann, R., Baksh, S., Gao, B., Minna, J.D., Downward, J., Maher, E.R., Latif, F. Cancer Res. (2003) [Pubmed]
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