DDX20 explained
Probable ATP-dependent RNA helicase DDX20, also known as DEAD-box helicase 20 and gem-associated protein 3 (GEMIN3), is an enzyme that in humans is encoded by the DDX20 gene.[1] [2]
Function
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which has an ATPase activity and is a component of the survival of motor neuron (SMN) complex. SMN is the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs.
Clinical significance
Previous research has revealed that DDX20 may act as a tumor suppressor in hepatocellular carcinoma and as a tumor promoter in breast cancer. DDX20 deficiency enhances NF-κB activity by impairing the NF-κB-suppressive action of microRNAs, and suggest that dysregulation of the microRNA machinery components may also be involved in pathogenesis in various human diseases.[3] Such as miRNA-140 which acts as a liver tumor suppressor, and due to a deficiency of DDX20, miRNA-140 function gets impair, this subsequent functional impairment of miRNAs could lead to hepatocarcinogenesis. Similarly,[4] DDX20 may promote the progression of Prostate cancer (PCa) through the NF-κB pathway.[5] In a clinical based study it has been observed that positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. It makes DP103 has potential as a therapeutic target for breast cancer treatment.[6]
Interactions
DDX20 has been shown to interact with:
- EIF2C2,[7]
- GEMIN4,[8] [9]
- GEMIN5,[8] [10]
- LSM2,[11]
- SMN1,[8] [11] [12]
- SNRPB,[11]
- SNRPD3[11] and
- SNRPG,[11]
- SNRPD1,[11]
- SNRPD2,[11]
- SNRPE,[11]
- SNRPF,[11] and
- SIP1.[8] [11]
Further reading
- Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–113 . April 1996 . 8619474 . 10.1006/abio.1996.0138 .
- Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . 6 . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–358 . April 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
- Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G . Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems . The Journal of Cell Biology . 147 . 6 . 1181–1194 . December 1999 . 10601333 . 2168095 . 10.1083/jcb.147.6.1181 .
- Charroux B, Pellizzoni L, Perkinson RA, Yong J, Shevchenko A, Mann M, Dreyfuss G . Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli . The Journal of Cell Biology . 148 . 6 . 1177–1186 . March 2000 . 10725331 . 2174312 . 10.1083/jcb.148.6.1177 .
- Meister G, Bühler D, Laggerbauer B, Zobawa M, Lottspeich F, Fischer U . Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins . Human Molecular Genetics . 9 . 13 . 1977–1986 . August 2000 . 10942426 . 10.1093/hmg/9.13.1977 . free .
- Pellizzoni L, Charroux B, Rappsilber J, Mann M, Dreyfuss G . A functional interaction between the survival motor neuron complex and RNA polymerase II . The Journal of Cell Biology . 152 . 1 . 75–85 . January 2001 . 11149922 . 2193649 . 10.1083/jcb.152.1.75 .
- Friesen WJ, Paushkin S, Wyce A, Massenet S, Pesiridis GS, Van Duyne G, Rappsilber J, Mann M, Dreyfuss G . 6 . The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins . Molecular and Cellular Biology . 21 . 24 . 8289–8300 . December 2001 . 11713266 . 99994 . 10.1128/MCB.21.24.8289-8300.2001 .
- Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G . Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins . The Journal of Biological Chemistry . 277 . 7 . 5631–5636 . February 2002 . 11714716 . 10.1074/jbc.M109448200 . free .
- Pellizzoni L, Baccon J, Rappsilber J, Mann M, Dreyfuss G . Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component . The Journal of Biological Chemistry . 277 . 9 . 7540–7545 . March 2002 . 11748230 . 10.1074/jbc.M110141200 . free .
- Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G . 6 . miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs . Genes & Development . 16 . 6 . 720–728 . March 2002 . 11914277 . 155365 . 10.1101/gad.974702 .
- Klappacher GW, Lunyak VV, Sykes DB, Sawka-Verhelle D, Sage J, Brard G, Ngo SD, Gangadharan D, Jacks T, Kamps MP, Rose DW, Rosenfeld MG, Glass CK . 6 . An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation . Cell . 109 . 2 . 169–180 . April 2002 . 12007404 . 10.1016/S0092-8674(02)00714-6 . 16359491 . free .
- Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G . Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex . The Journal of Biological Chemistry . 277 . 35 . 31957–31962 . August 2002 . 12065586 . 10.1074/jbc.M203478200 . free .
- Narayanan U, Ospina JK, Frey MR, Hebert MD, Matera AG . SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta . Human Molecular Genetics . 11 . 15 . 1785–1795 . July 2002 . 12095920 . 1630493 . 10.1093/hmg/11.15.1785 .
- Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM . Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region . Genomics . 83 . 1 . 153–167 . January 2004 . 14667819 . 10.1016/S0888-7543(03)00235-0 .
- Nelson PT, Hatzigeorgiou AG, Mourelatos Z . miRNP:mRNA association in polyribosomes in a human neuronal cell line . RNA . 10 . 3 . 387–394 . March 2004 . 14970384 . 1370934 . 10.1261/rna.5181104 .
- Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . 6 . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–12135 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . free . 2004PNAS..10112130B .
Notes and References
- Grundhoff AT, Kremmer E, Türeci O, Glieden A, Gindorf C, Atz J, Mueller-Lantzsch N, Schubach WH, Grässer FA . 6 . Characterization of DP103, a novel DEAD box protein that binds to the Epstein-Barr virus nuclear proteins EBNA2 and EBNA3C . The Journal of Biological Chemistry . 274 . 27 . 19136–19144 . July 1999 . 10383418 . 10.1074/jbc.274.27.19136 . free .
- Web site: Entrez Gene: DDX20 DEAD (Asp-Glu-Ala-Asp) box polypeptide 20.
- Takata A, Otsuka M, Yoshikawa T, Kishikawa T, Kudo Y, Goto T, Yoshida H, Koike K . 6 . A miRNA machinery component DDX20 controls NF-κB via microRNA-140 function . Biochemical and Biophysical Research Communications . 420 . 3 . 564–569 . April 2012 . 22445758 . 10.1016/j.bbrc.2012.03.034 .
- Takata A, Otsuka M, Yoshikawa T, Kishikawa T, Hikiba Y, Obi S, Goto T, Kang YJ, Maeda S, Yoshida H, Omata M, Asahara H, Koike K . 6 . MicroRNA-140 acts as a liver tumor suppressor by controlling NF-κB activity by directly targeting DNA methyltransferase 1 (Dnmt1) expression . Hepatology . 57 . 1 . 162–170 . January 2013 . 22898998 . 3521841 . 10.1002/hep.26011 .
- Chen W, Zhou P, Li X . High expression of DDX20 enhances the proliferation and metastatic potential of prostate cancer cells through the NF-κB pathway . International Journal of Molecular Medicine . 37 . 6 . 1551–1557 . June 2016 . 27121695 . 4866965 . 10.3892/ijmm.2016.2575 .
- Shin EM, Hay HS, Lee MH, Goh JN, Tan TZ, Sen YP, Lim SW, Yousef EM, Ong HT, Thike AA, Kong X, Wu Z, Mendoz E, Sun W, Salto-Tellez M, Lim CT, Lobie PE, Lim YP, Yap CT, Zeng Q, Sethi G, Lee MB, Tan P, Goh BC, Miller LD, Thiery JP, Zhu T, Gaboury L, Tan PH, Hui KM, Yip GW, Miyamoto S, Kumar AP, Tergaonkar V . 6 . DEAD-box helicase DP103 defines metastatic potential of human breast cancers . The Journal of Clinical Investigation . 124 . 9 . 3807–3824 . September 2014 . 25083991 . 4151228 . 10.1172/JCI73451 .
- Nelson PT, Hatzigeorgiou AG, Mourelatos Z . miRNP:mRNA association in polyribosomes in a human neuronal cell line . RNA . 10 . 3 . 387–394 . March 2004 . 14970384 . 1370934 . 10.1261/rna.5181104 .
- Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G . 6 . miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs . Genes & Development . 16 . 6 . 720–728 . March 2002 . 11914277 . 155365 . 10.1101/gad.974702 .
- Charroux B, Pellizzoni L, Perkinson RA, Yong J, Shevchenko A, Mann M, Dreyfuss G . Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli . The Journal of Cell Biology . 148 . 6 . 1177–1186 . March 2000 . 10725331 . 2174312 . 10.1083/jcb.148.6.1177 .
- Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G . Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins . The Journal of Biological Chemistry . 277 . 7 . 5631–5636 . February 2002 . 11714716 . 10.1074/jbc.M109448200 . free .
- Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G . Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems . The Journal of Cell Biology . 147 . 6 . 1181–1194 . December 1999 . 10601333 . 2168095 . 10.1083/jcb.147.6.1181 .
- Meister G, Bühler D, Laggerbauer B, Zobawa M, Lottspeich F, Fischer U . Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins . Human Molecular Genetics . 9 . 13 . 1977–1986 . August 2000 . 10942426 . 10.1093/hmg/9.13.1977 . free .