MADD (gene) explained

MAP kinase-activating death domain protein is an enzyme that in humans is encoded by the MADD gene.^{[1] [2] [3]}

Tumor necrosis factor alpha (TNF-alpha) is a signaling molecule that interacts with one of two receptors on cells targeted for apoptosis. The apoptotic signal is transduced inside these cells by cytoplasmic adaptor proteins. The protein encoded by this gene is a death domain-containing adaptor protein that interacts with the death domain of TNF-alpha receptor 1 to activate mitogen-activated protein kinase (MAPK) and propagate the apoptotic signal. It is membrane-bound and expressed at a higher level in neoplastic cells than in normal cells. Several transcript variants encoding different isoforms have been described for this gene. MADD is mostly expressed in the cell membrane with some cytoplasmic expression in human cells.^[4]

Further reading

• Chow VT, Lee SS . DENN, a novel human gene differentially expressed in normal and neoplastic cells . DNA Seq. . 6 . 5 . 263–73 . 1997 . 8988362 . 10.3109/10425179609020873 .
• Nagase T, Ishikawa K, Nakajima D, etal . Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro . DNA Res. . 4 . 2 . 141–50 . 1997 . 9205841 . 10.1093/dnares/4.2.141 . free .
• Zhang Y, Zhou L, Miller CA . A splicing variant of a death domain protein that is regulated by a mitogen-activated kinase is a substrate for c-Jun N-terminal kinase in the human central nervous system . Proc. Natl. Acad. Sci. U.S.A. . 95 . 5 . 2586–91 . 1998 . 9482930 . 10.1073/pnas.95.5.2586 . 19423 . 1998PNAS...95.2586Z . free .
• Suzuki Y, Ishihara D, Sasaki M, etal . Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries . Genomics . 64 . 3 . 286–97 . 2000 . 10756096 . 10.1006/geno.2000.6076 .
• Telliez JB, Bean KM, Lin LL . LRDD, a novel leucine rich repeat and death domain containing protein . Biochim. Biophys. Acta . 1478 . 2 . 280–8 . 2000 . 10825539 . 10.1016/S0167-4838(00)00029-7 .
• Iwasaki K, Toyonaga R . The Rab3 GDP/GTP exchange factor homolog AEX-3 has a dual function in synaptic transmission . EMBO J. . 19 . 17 . 4806–16 . 2000 . 10970871 . 10.1093/emboj/19.17.4806 . 302062 .
• Al-Zoubi AM, Efimova EV, Kaithamana S, etal . Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3 . J. Biol. Chem. . 276 . 50 . 47202–11 . 2002 . 11577081 . 10.1074/jbc.M104835200 . free .
• Lim KM, Chow VT . Induction of marked apoptosis in mammalian cancer cell lines by antisense DNA treatment to abolish expression of DENN (differentially expressed in normal and neoplastic cells) . Mol. Carcinog. . 35 . 3 . 110–26 . 2002 . 12410563 . 10.1002/mc.10082 . 21107199 .
• Nakayama M, Kikuno R, Ohara O . Protein–Protein Interactions Between Large Proteins: Two-Hybrid Screening Using a Functionally Classified Library Composed of Long cDNAs . Genome Res. . 12 . 11 . 1773–84 . 2003 . 12421765 . 10.1101/gr.406902 . 187542 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Efimova E, Martinez O, Lokshin A, etal . IG20, a MADD splice variant, increases cell susceptibility to gamma-irradiation and induces soluble mediators that suppress tumor cell growth . Cancer Res. . 63 . 24 . 8768–76 . 2004 . 14695193 .
• Efimova EV, Al-Zoubi AM, Martinez O, etal . IG20, in contrast to DENN-SV, (MADD splice variants) suppresses tumor cell survival, and enhances their susceptibility to apoptosis and cancer drugs . Oncogene . 23 . 5 . 1076–87 . 2004 . 14716293 . 10.1038/sj.onc.1207210 . free .
• Lim KM, Yeo WS, Chow VT . Antisense abrogation of DENN expression induces apoptosis of leukemia cells in vitro, causes tumor regression in vivo and alters the transcription of genes involved in apoptosis and the cell cycle . Int. J. Cancer . 109 . 1 . 24–37 . 2004 . 14735464 . 10.1002/ijc.11660 . 10327890 . free .
• Del Villar K, Miller CA . Down-regulation of DENN/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer's disease brain and hippocampal neurons . Proc. Natl. Acad. Sci. U.S.A. . 101 . 12 . 4210–5 . 2004 . 15007167 . 10.1073/pnas.0307349101 . 384720 . 2004PNAS..101.4210D . free .
• Xu Y, Kulkosky J, Acheampong E, etal . HIV-1-mediated apoptosis of neuronal cells: Proximal molecular mechanisms of HIV-1-induced encephalopathy . Proc. Natl. Acad. Sci. U.S.A. . 101 . 18 . 7070–5 . 2004 . 15103018 . 10.1073/pnas.0304859101 . 406467 . 2004PNAS..101.7070X . free .
• Ramaswamy M, Efimova EV, Martinez O, etal . IG20 (MADD splice variant-5), a proapoptotic protein, interacts with DR4/DR5 and enhances TRAIL-induced apoptosis by increasing recruitment of FADD and caspase-8 to the DISC . Oncogene . 23 . 36 . 6083–94 . 2005 . 15208670 . 10.1038/sj.onc.1207804 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Hu YF, Zhang HL, Cai T, etal . The IA-2 interactome . Diabetologia . 48 . 12 . 2576–81 . 2006 . 16273344 . 10.1007/s00125-005-0037-y . 9765497 . free .

Notes and References

1. Schievella AR, Chen JH, Graham JR, Lin LL . MADD, a novel death domain protein that interacts with the type 1 tumor necrosis factor receptor and activates mitogen-activated protein kinase . J Biol Chem . 272 . 18 . 12069–75 . Jun 1997 . 9115275 . 10.1074/jbc.272.18.12069 . free .
2. Chow VT, Lim KM, Lim D . The human DENN gene: genomic organization, alternative splicing, and localization to chromosome 11p11.21-p11.22 . Genome . 41 . 4 . 543–52 . Nov 1998 . 9796103 . 10.1139/g98-050 .
3. Web site: Entrez Gene: MADD MAP-kinase activating death domain.
4. Chow, V. T., & Lee, S. S. (1996). DENN, a novel human gene differentially expressed in normal and neoplastic cells. DNA sequence : the journal of DNA sequencing and mapping, 6(5), 263–273. https://doi.org/10.3109/10425179609020873