MCF2 explained

Proto-oncogene DBL is a protein that in humans is encoded by the MCF2 gene.^{[1] [2] [3]}

The commonly-used name DBL is derived from “diffuse B-cell lymphoma”, the cancer type where this gene was first identified as an oncogene,^[4] while the name MCF2 name derives from “MCF.2 cell line-derived transforming sequence”.^[5]

DBL is the founding member of a large family of guanine nucleotide exchange factors that share a common DBL-homology (DH) domain), so DBL is also named as a member of this RhoGEF family as ARHGEF21. DH domains function to activate small GTPases of the Rho family by facilitating release of GDP from an inactive Rho GTPase and binding of GTP to activate it. In particular, DBL activates the Rho family member Cdc42.^[6]

Gene recombinations that result in the loss of N-terminal regions produce MCF2 variants with oncogenic activity.[supplied by OMIM]

Further reading

• Ron D, Zannini M, Lewis M, Wickner RB, Hunt LT, Graziani G, Tronick SR, Aaronson SA, Eva A . 6 . A region of proto-dbl essential for its transforming activity shows sequence similarity to a yeast cell cycle gene, CDC24, and the human breakpoint cluster gene, bcr . The New Biologist . 3 . 4 . 372–9 . April 1991 . 2065022 .
• Tronick SR, McBride OW, Popescu NC, Eva A . Chromosomal localization of DBL oncogene sequences . Genomics . 5 . 3 . 546–53 . October 1989 . 2613238 . 10.1016/0888-7543(89)90022-0 .
• Ron D, Tronick SR, Aaronson SA, Eva A . Molecular cloning and characterization of the human dbl proto-oncogene: evidence that its overexpression is sufficient to transform NIH/3T3 cells . The EMBO Journal . 7 . 8 . 2465–73 . August 1988 . 3056717 . 457116 . 10.1002/j.1460-2075.1988.tb03093.x.
• Eva A, Vecchio G, Rao CD, Tronick SR, Aaronson SA . The predicted DBL oncogene product defines a distinct class of transforming proteins . Proceedings of the National Academy of Sciences of the United States of America . 85 . 7 . 2061–5 . April 1988 . 3281159 . 279928 . 10.1073/pnas.85.7.2061 . 1988PNAS...85.2061E . free .
• Srivastava SK, Wheelock RH, Aaronson SA, Eva A . Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene . Proceedings of the National Academy of Sciences of the United States of America . 83 . 23 . 8868–72 . December 1986 . 3491366 . 387034 . 10.1073/pnas.83.23.8868 . 1986PNAS...83.8868S . free .
• Hart MJ, Eva A, Zangrilli D, Aaronson SA, Evans T, Cerione RA, Zheng Y . Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product . The Journal of Biological Chemistry . 269 . 1 . 62–5 . January 1994 . 10.1016/S0021-9258(17)42313-1 . 8276860 . free .
• Nishida K, Kaziro Y, Satoh T . Association of the proto-oncogene product dbl with G protein betagamma subunits . FEBS Letters . 459 . 2 . 186–90 . October 1999 . 10518015 . 10.1016/S0014-5793(99)01244-2 . 83524892 .
• Kato J, Kaziro Y, Satoh T . Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation . Biochemical and Biophysical Research Communications . 268 . 1 . 141–7 . February 2000 . 10652228 . 10.1006/bbrc.2000.2106 .
• Zhu K, Debreceni B, Li R, Zheng Y . Identification of Rho GTPase-dependent sites in the Dbl homology domain of oncogenic Dbl that are required for transformation . The Journal of Biological Chemistry . 275 . 34 . 25993–6001 . August 2000 . 10854437 . 10.1074/jbc.M003780200 . free .
• Palmieri G, de Franciscis V, Casamassimi A, Romano G, Torino A, Pingitore P, Califano D, Santelli G, Eva A, Vecchio G, D'Urso M, Ciccodicola A . 6 . Human dbl proto-oncogene in 85 kb of xq26, and determination of the transcription initiation site . Gene . 253 . 1 . 107–15 . July 2000 . 10925207 . 10.1016/S0378-1119(00)00212-2 .
• Jin S, Exton JH . Activation of RhoA by association of Galpha(13) with Dbl . Biochemical and Biophysical Research Communications . 277 . 3 . 718–21 . November 2000 . 11062019 . 10.1006/bbrc.2000.3744 .
• Zhu K, Debreceni B, Bi F, Zheng Y . Oligomerization of DH domain is essential for Dbl-induced transformation . Molecular and Cellular Biology . 21 . 2 . 425–37 . January 2001 . 11134331 . 86589 . 10.1128/MCB.21.2.425-437.2001 .
• Vanni C, Mancini P, Gao Y, Ottaviano C, Guo F, Salani B, Torrisi MR, Zheng Y, Eva A . 6 . Regulation of proto-Dbl by intracellular membrane targeting and protein stability . The Journal of Biological Chemistry . 277 . 22 . 19745–53 . May 2002 . 11907027 . 10.1074/jbc.M111025200 . free .
• Wennerberg K, Ellerbroek SM, Liu RY, Karnoub AE, Burridge K, Der CJ . RhoG signals in parallel with Rac1 and Cdc42 . The Journal of Biological Chemistry . 277 . 49 . 47810–7 . December 2002 . 12376551 . 10.1074/jbc.M203816200 . free .
• Komai K, Okayama R, Kitagawa M, Yagi H, Chihara K, Shiozawa S . Alternative splicing variants of the human DBL (MCF-2) proto-oncogene . Biochemical and Biophysical Research Communications . 299 . 3 . 455–8 . December 2002 . 12445822 . 10.1016/S0006-291X(02)02645-1 . 20.500.14094/D2002682 . free .
• Komai K, Mukae-Sakairi N, Kitagawa M, Shiozawa S . Characterization of novel splicing variants of the mouse MCF-2 (DBL) proto-oncogene . Biochemical and Biophysical Research Communications . 309 . 4 . 906–9 . October 2003 . 13679059 . 10.1016/j.bbrc.2003.08.088 . 26656167 . 2020-09-08 . 2018-11-02 . https://web.archive.org/web/20181102002724/http://www.lib.kobe-u.ac.jp/repository/90000273.pdf . dead .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . 6 . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .

Notes and References

1. Noguchi T, Galland F, Batoz M, Mattei MG, Birnbaum D . Activation of a mcf.2 oncogene by deletion of amino-terminal coding sequences . Oncogene . 3 . 6 . 709–15 . December 1988 . 2577874 .
2. Galland F, Stefanova M, Lafage M, Birnbaum D . Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15----q23 . Cytogenetics and Cell Genetics . 60 . 2 . 114–6 . Jul 1992 . 1611909 . 10.1159/000133316 .
3. Web site: Entrez Gene: MCF2 MCF.2 cell line derived transforming sequence.
4. Eva A, Aaronson SA . Isolation of a new human oncogene from a diffuse B-cell lymphoma . Nature . 316 . 6025 . 273–5 . 1985-07-18 . 3875039 . 10.1038/316273a0 . 1985Natur.316..273E . 4268140 .
5. Noguchi T, Mattei MG, Oberlè I, Planche J, Imbert J, Pelassy C, Birg F, Birnbaum D . 6 . Localization of the mcf.2 transforming sequence to the X chromosome . The EMBO Journal . 6 . 5 . 1301–7 . May 1987 . 3038515 . 553933 . 10.1002/j.1460-2075.1987.tb02368.x .
6. Fort P, Blangy A . The Evolutionary Landscape of Dbl-Like RhoGEF Families: Adapting Eukaryotic Cells to Environmental Signals . Genome Biology and Evolution . 9 . 6 . 1471–1486 . June 2017 . 28541439 . 5499878 . 10.1093/gbe/evx100 .