Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

RASSF6

  • Hiroaki Iwasa
  • Takanobu Shimizu
  • Yutaka Hata
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101773

Synonyms

Historical Background

Human RASSF6 gene is registered as one of the Ras-association domain family in the databank. RASSF6 was first referred in the paper reporting the association of SNPs in RASSF6 with susceptibility to respiratory syncytial virus bronchiolitis (Hull et al. 2004). The researchers discussed based on the structural feature and the potential function of RASSF6 in the regulation of cytoskeletal structure, gene expression, and cell-cell interactions. Thereafter, RASSF6 was identified as an interactor with a junctional protein named membrane-associated guanylate kinase with an inverted arrangement of protein-protein interaction domains (MAGI1) (Ikeda et al. 2007). RASSF6 was also identified from the EST database by tblastn using the Ras-association (RA) domain of RASSF1 (Allen et al. 2007).

Structure of RASSF6

In the GenBank database, four...
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References

  1. Allen NP, Donninger H, Vos MD, Eckfeld K, Hesson L, Gordon L, et al. RASSF6 is a novel member of the RASSF family of tumor suppressors. Oncogene. 2007;26:6203–11.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Chan JJ, Flatters D, Rodrigues-Lima F, Yan J, Thalassinos K, Katan M. Comparative analysis of interactions of RASSF1-10. Adv Biol Regul. 2013;53:190–201.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Djos A, Martinsson T, Kogner P, Carén H. The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma. Mol Cancer. 2012;11:40.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Guo W, Dong Z, Guo Y, Shen S, Guo X, Kuang G, et al. Decreased expression and frequent promoter hypermethylation of RASSF2 and RASSF6 correlate with malignant progression and poor prognosis of gastric cardia adenocarcinoma. Mol Carcinog. 2015;  https://doi.org/10.1002/mc.22416.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Harvey KF, Pfleger CM, Hariharan IK. The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell. 2003;114:457–67.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Hesson LB, Dunwell TL, Cooper WN, Catchpoole D, Brini AT, Chiaramonte R, et al. The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias. Mol Cancer. 2009;8:42.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Huang J, Wu S, Barrera J, Matthews K, Pan D. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila homolog of YAP. Cell. 2005;122:421–34.CrossRefPubMedGoogle Scholar
  8. Hull J, Rowlands K, Lockhart E, Sharland M, Moore C, Hanchard N, et al. Haplotype mapping of the bronchiolitis susceptibility locus near IL8. Hum Genet. 2004;114:272–9.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Ikeda M, Hirabayashi S, Fujiwara N, Mori H, Kawata A, Iida J, et al. Ras-association domain family protein 6 induces apoptosis via both caspase-dependent and caspase-independent pathways. Exp Cell Res. 2007;313:1484–95.CrossRefPubMedGoogle Scholar
  10. Ikeda M, Kawata A, Nishikawa M, Tateishi Y, Yamaguchi M, Nakagawa K, et al. Hippo pathway-dependent and -independent roles of RASSF6. Sci Signal. 2009;2(90):ra59.  https://doi.org/10.1126/scisignal.2000300.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Iwasa H, Kudo T, Maimaiti S, Ikeda M, Maruyama J, Nakagawa K, et al. The RASSF6 tumor suppressor protein regulates apoptosis and the cell cycle via MDM2 protein and p53 protein. J Biol Chem. 2013;288:30320–9.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Iwasa H, Jiang X, Hata Y. RASSF6: the putative tumor suppressor of the RASSF family. Cancers (Basel). 2015;7(4):2415–26.CrossRefGoogle Scholar
  13. Justice RW, Zilian O, Woods DF, Noll M, Bryant PJ. The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 1995;9:534–46.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Kodaka M, Hata Y. The mammalian Hippo pathway: regulation and function of YAP1 and TAZ. Cell Mol Life Sci. 2015;72:285–306.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Lai ZC, Wei X, Shimizu T, Ramos E, Rohrbaugh M, Nikolaidis N, et al. Control of cell proliferation and apoptosis by mob as tumor suppressor, mats. Cell. 2005;120:675–85.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Liang YY, Zheng LS, Wu YZ, Peng LX, Cao Y, Cao X, et al. RASSF6 promotes p21(Cip1/Waf1)-dependent cell cycle arrest and apoptosis through activation of the JNK/SAPK pathway in clear cell renal cell carcinoma. Cell Cycle. 2014;13:1440–9.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Meng W, Huebner A, Shabsigh A, Chakravarti A, Lautenschlaeger T. Combined RASSF1A and RASSF2A promoter methylation analysis as diagnostic biomarker for bladder cancer. Mol Biol Int. 2012;2012:701814.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Mezzanotte JJ, Hill V, Schmidt ML, Shinawi T, Tommasi S, Krex D, et al. RASSF6 exhibits promoter hypermethylation in metastatic melanoma and inhibits invasion in melanoma cells. Epigenetics. 2014;9:1496–503.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Pan D. The hippo signaling pathway in development and cancer. Dev Cell. 2010;19(4):491–505.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Pantalacci S, Tapon N, Léopold P. The Salvador partner Hippo promotes apoptosis and cell-cycle exit in Drosophila. Nat Cell Biol. 2003;5:921–7.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Polesello C, Huelsmann S, Brown NH, Tapon N. The Drosophila RASSF homolog antagonizes the hippo pathway. Curr Biol. 2006;16:2459–65.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Rawat SJ, Chernoff J. Regulation of mammalian Ste20 (Mst) kinases. Trends Biochem Sci. 2015;40:149–56.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Richter AM, Pfeifer GP, Dammann RH. The RASSF proteins in cancer: from epigenetic silencing to functional characterization. Biochim Biophys Acta. 2009;1796:114–28.PubMedPubMedCentralGoogle Scholar
  24. Richter AM, Zimmermann T, Haag T, Walesch SK, Dammann RH. Promoter methylation status of Ras-association domain family members in pheochromocytoma. Front Endocrinol (Lausanne). 2015;6:21.Google Scholar
  25. Sanada Y, Kumoto T, Suehiro H, Nishimura F, Kato N, Hata Y, et al. RASSF6 expression in adipocytes is down-regulated by interaction with macrophages. PLoS One. 2013;8(4):e61931.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Shinawi T, Hill V, Dagklis A, Baliakas P, Stamatopoulos K, Agathanggelou A, et al. KIBRA gene methylation is associated with unfavorable biological prognostic parameters in chronic lymphocytic leukemia. Epigenetics. 2012;7:211–5.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Tapon N, Harvey KF, Bell DW, Wahrer DC, Schiripo TA, Haber D, et al. Salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell. 2002;110:467–78.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Udan RS, Kango-Singh M, Nolo R, Tao C, Halder G. Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat Cell Biol. 2003;5:914–20.PubMedPubMedCentralCrossRefGoogle Scholar
  29. van Keimpema M, Grüneberg LJ, Mokry M, van Boxtel R, Koster J, Coffer PJ, et al. FOXP1 directly represses transcription of proapoptotic genes and cooperates with NF-κB to promote survival of human B cells. Blood. 2014;124:3431–40.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Wen Y, Wang Q, Zhou C, Yan D, Qiu G, Yang C, et al. Decreased expression of RASSF6 is a novel independent prognostic marker of a worse outcome in gastric cancer patients after curative surgery. Ann Surg Oncol. 2011;18:3858–67.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Withanage K, Nakagawa K, Ikeda M, Kurihara H, Kudo T, Yang Z, et al. Expression of RASSF6 in kidney and the implication of RASSF6 and the Hippo pathway in the sorbitol-induced apoptosis in renal proximal tubular epithelial cells. J Biochem. 2012;152:111–9.CrossRefPubMedGoogle Scholar
  32. Wu S, Huang J, Dong J, Pan D. Hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell. 2003;114:445–56.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Ye HL, Li DD, Lin Q, Zhou Y, Zhou QB, Zeng B, et al. Low RASSF6 expression in pancreatic ductal adenocarcinoma is associated with poor survival. World J Gastroenterol. 2015;21:6621–30.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Yu FX, Guan KL. The Hippo pathway: regulators and regulations. Genes Dev. 2013;27:355–71.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Medical Biochemistry, Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Center for Brain Integration ResearchTokyo Medical and Dental UniversityTokyoJapan