DDX3X
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ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the DDX3X gene.[3][4][5]
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 interacts specifically with hepatitis C virus core protein resulting a change in intracellular location. This gene has a homolog located in the nonrecombining region of the Y chromosome. The protein sequence is 91% identical between this gene and the Y-linked homolog.[5]
Role in cancer
DDX3X is involved in many different types of cancer. For example, it is abnormally expressed in breast epithelial cancer cells in which its expression is activated by HIF1A during hypoxia.[6] Increased expression of DDX3X by HIF1A in hypoxia is initiated by the direct binding of HIF1A to the HIF1A response element,[6] as verified with chromatin immunoprecipitation and luciferase reporter assay. Since the expression of DDX3X is affected by the activity of HIF1A, the co-localization of these proteins has also been demonstrated in MDA-MB-231 xenograft tumor samples.[6]
In HeLa cells DDX3X is reported to control cell cycle progression through Cyclin E1.[7] More specifically, DDX3X was shown to directly bind to the 5´ UTR of Cyclin E1 and thereby facilitating the translation of the protein. Increased protein levels of Cyclin E1 was demonstrated to mediate the transition of S phase entry.[7]
Clinical significance
Mutations of the DDX3X gene are also associated with medulloblastoma.[8][9][10]
References
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ Lahn BT, Page DC (Nov 1997). "Functional coherence of the human Y chromosome". Science. 278 (5338): 675–680. doi:10.1126/science.278.5338.675. PMID 9381176.
- ↑ Park SH, Lee SG, Kim Y, Song K (Oct 1998). "Assignment of a human putative RNA helicase gene, DDX3, to human X chromosome bands p11.3→p11.23". Cytogenet Cell Genet. 81 (3–4): 178–179. doi:10.1159/000015022. PMID 9730595.
- 1 2 "Entrez Gene: DDX3X DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked".
- 1 2 3 "Expression of DDX3 is directly modulated by hypoxia inducible factor-1 alpha in breast epithelial cells". PLoS ONE. 2011-03-23. doi:10.1371/journal.pone.0017563.
- 1 2 "DDX3 Regulates Cell Growth through Translational Control of Cyclin E1". Molecular and Cellular Biology. November 2010. doi:10.1128/MCB.00560-10.
- ↑ Robinson G, Parker M, Kranenburg TA, et al. (June 2012). "Novel mutations target distinct subgroups of medulloblastoma". Nature. 488 (7409). doi:10.1038/nature11213.
- ↑ Jones TW, Jäger N, Kool M, et al. (July 2012). "Dissecting the genomic complexity underlying medulloblastoma". Nature. 488 (7409): 100–5. doi:10.1038/nature11284. PMC 3662966
. PMID 22832583.
- ↑ Pugh TJ, Weeraratne SD, Archer TC, et al. (July 2012). "Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations". Nature. doi:10.1038/nature11329.
Further reading
- Li L, Li HS, Pauza CD, et al. (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Res. 15 (11–12): 923–934. doi:10.1038/sj.cr.7290370. PMID 16354571.
- Owsianka AM, Patel AH (1999). "Hepatitis C virus core protein interacts with a human DEAD box protein DDX3". Virology. 257 (2): 330–340. doi:10.1006/viro.1999.9659. PMID 10329544.
- Mamiya N, Worman HJ (1999). "Hepatitis C virus core protein binds to a DEAD box RNA helicase". J. Biol. Chem. 274 (22): 15751–15756. doi:10.1074/jbc.274.22.15751. PMID 10336476.
- Yagüe J, Alvarez I, Rognan D, et al. (2000). "An N-acetylated natural ligand of human histocompatibility leukocyte antigen (HLA)-B39. Classical major histocompatibility complex class I proteins bind peptides with a blocked NH(2) terminus in vivo". J. Exp. Med. 191 (12): 2083–2092. doi:10.1084/jem.191.12.2083. PMC 2193201
. PMID 10859333.
- Kim YS, Lee SG, Park SH, Song K (2002). "Gene structure of the human DDX3 and chromosome mapping of its related sequences". Mol. Cells. 12 (2): 209–14. PMID 11710523.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241
. PMID 12477932.
- Li J, Hawkins IC, Harvey CD, et al. (2003). "Regulation of alternative splicing by SRrp86 and its interacting proteins". Mol. Cell. Biol. 23 (21): 7437–7447. doi:10.1128/MCB.23.21.7437-7447.2003. PMC 207616
. PMID 14559993.
- Shu H, Chen S, Bi Q, et al. (2004). "Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line". Mol. Cell Proteomics. 3 (3): 279–286. doi:10.1074/mcp.D300003-MCP200. PMID 14729942.
- Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928
. PMID 15489334.
- Yedavalli VS, Neuveut C, Chi YH, et al. (2004). "Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function". Cell. 119 (3): 381–392. doi:10.1016/j.cell.2004.09.029. PMID 15507209.
- Dayton AI (2006). "Within you, without you: HIV-1 Rev and RNA export". Retrovirology. 1: 35. doi:10.1186/1742-4690-1-35. PMC 526764
. PMID 15516266.
- Krishnan V, Zeichner SL (2006). "Alterations in the expression of DEAD-box and other RNA binding proteins during HIV-1 replication". Retrovirology. 1: 42. doi:10.1186/1742-4690-1-42. PMC 543576
. PMID 15588285.
- Rush J, Moritz A, Lee KA, et al. (2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nat. Biotechnol. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455.
- Tao WA, Wollscheid B, O'Brien R, et al. (2005). "Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry". Nat. Methods. 2 (8): 591–598. doi:10.1038/nmeth776. PMID 16094384.
- Gevaert K, Staes A, Van Damme J, et al. (2006). "Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC". Proteomics. 5 (14): 3589–3599. doi:10.1002/pmic.200401217. PMID 16097034.
- Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. doi:10.1038/nature04209. PMID 16189514.
- Chang PC, Chi CW, Chau GY, et al. (2006). "DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control". Oncogene. 25 (14): 1991–2003. doi:10.1038/sj.onc.1209239. PMID 16301996.