DDX20

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
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RefSeq (mRNA)

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RefSeq (protein)

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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.[2] This DEAD box protein is one of the gem-associated proteins (GEMIN3) that interacts directly with SMN.[3] SMN is the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs.[2]

Biological Implication

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.[4] 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,[5] DDX20 may promote the progression of Prostate cancer (PCa) through the NF-κB pathway.[6] 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.[7]

Interactions

DDX20 has been shown to interact with:

References

  1. Grundhoff AT, Kremmer E, Türeci O, Glieden A, Gindorf C, Atz J, Mueller-Lantzsch N, Schubach WH, Grässer FA (July 1999). "Characterization of DP103, a novel DEAD box protein that binds to the Epstein-Barr virus nuclear proteins EBNA2 and EBNA3C". J Biol Chem. 274 (27): 19136–44. doi:10.1074/jbc.274.27.19136. PMID 10383418.
  2. 2.0 2.1 2.2 "Entrez Gene: DDX20 DEAD (Asp-Glu-Ala-Asp) box polypeptide 20".
  3. Seng, CO; Magee, C; Young, PJ; Lorson, CL; Allen, JP (15 April 2015). "The SMN structure reveals its crucial role in snRNP assembly". Human Molecular Genetics. 24 (8): 2138–46. doi:10.1093/hmg/ddu734. PMID 25561692.
  4. Takata, Akemi; Otsuka, Motoyuki; Yoshikawa, Takeshi; Kishikawa, Takahiro; Kudo, Yotaro; Goto, Tadashi; Yoshida, Haruhiko; Koike, Kazuhiko (2012-04-13). "A miRNA machinery component DDX20 controls NF-κB via microRNA-140 function". Biochemical and Biophysical Research Communications. 420 (3): 564–569. doi:10.1016/j.bbrc.2012.03.034. ISSN 1090-2104. PMID 22445758.
  5. Takata, Akemi; Otsuka, Motoyuki; Yoshikawa, Takeshi; Kishikawa, Takahiro; Hikiba, Yohko; Obi, Shuntaro; Goto, Tadashi; Kang, Young Jun; Maeda, Shin (January 2013). "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. doi:10.1002/hep.26011. ISSN 1527-3350. PMC 3521841. PMID 22898998.
  6. Chen, Weiguo; Zhou, Peng; Li, Xiaowei (June 2016). "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. doi:10.3892/ijmm.2016.2575. ISSN 1791-244X. PMC 4866965. PMID 27121695.
  7. Shin, Eun Myoung; Hay, Hui Sin; Lee, Moon Hee; Goh, Jen Nee; Tan, Tuan Zea; Sen, Yin Ping; Lim, See Wee; Yousef, Einas M.; Ong, Hooi Tin (September 2014). "DEAD-box helicase DP103 defines metastatic potential of human breast cancers". The Journal of Clinical Investigation. 124 (9): 3807–3824. doi:10.1172/JCI73451. ISSN 1558-8238. PMC 4151228. PMID 25083991.
  8. 8.0 8.1 8.2 8.3 8.4 Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G (March 2002). "miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs". Genes Dev. 16 (6): 720–8. doi:10.1101/gad.974702. PMC 155365. PMID 11914277.
  9. Nelson PT, Hatzigeorgiou AG, Mourelatos Z (March 2004). "miRNP:mRNA association in polyribosomes in a human neuronal cell line". RNA. 10 (3): 387–94. doi:10.1261/rna.5181104. PMC 1370934. PMID 14970384.
  10. 10.0 10.1 Carnegie GK, Sleeman JE, Morrice N, Hastie CJ, Peggie MW, Philp A, Lamond AI, Cohen PT (May 2003). "Protein phosphatase 4 interacts with the Survival of Motor Neurons complex and enhances the temporal localisation of snRNPs". J. Cell Sci. 116 (Pt 10): 1905–13. doi:10.1242/jcs.00409. PMID 12668731.
  11. Charroux B, Pellizzoni L, Perkinson RA, Yong J, Shevchenko A, Mann M, Dreyfuss G (March 2000). "Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli". J. Cell Biol. 148 (6): 1177–86. doi:10.1083/jcb.148.6.1177. PMC 2174312. PMID 10725331.
  12. Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G (February 2002). "Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins". J. Biol. Chem. 277 (7): 5631–6. doi:10.1074/jbc.M109448200. PMID 11714716.
  13. 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 13.9 Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G (December 1999). "Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems". J. Cell Biol. 147 (6): 1181–94. doi:10.1083/jcb.147.6.1181. PMC 2168095. PMID 10601333.
  14. Meister G, Bühler D, Laggerbauer B, Zobawa M, Lottspeich F, Fischer U (August 2000). "Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins". Hum. Mol. Genet. 9 (13): 1977–86. doi:10.1093/hmg/9.13.1977. PMID 10942426.

Further reading


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