Disease relevance of DDX6

• The human DDX6 gene (alias RCK) at chromosome 11 band q23 was identified through the study of the breakpoint of t(11;14)(q23;q32) translocation in a B-cell lymphoma cell line, RC-K8 [1].
• This functional conservation, together with the common replication strategies of positive-stranded RNA viruses, suggests that RCK/p54 may also play a role in the replication of positive-stranded RNA viruses that infect humans [2].
• Xenopus Xp54 and Human RCK/p54 Helicases Functionally Replace Yeast Dhh1p in Brome Mosaic Virus RNA Replication [2].
• Structure of the RCK domain from the E. coli K+ channel and demonstration of its presence in the human BK channel [3].
• Paraffin sections of 49 invasive breast carcinomas and 40 benign lesions were examined by the avidin-biotin complex immunoperoxidase technique using two commercially available keratin 19-specific monoclonal antibodies, BA17 and RCK 108 [4].

High impact information on DDX6

• The channel's eight ligand-binding domains, the RCK domains, form an octameric gating ring in which Ca(2+) binding induces conformational changes that open the channel [5].
• These results provide insights into the quaternary organization of the KtrAB transporter and its mechanism of activation and show that the RCK-domain octameric ring model is generally applicable to other ion-transport systems [6].
• Eight RCK domains (regulators of K(+) conductance) form a gating ring at the intracellular membrane surface [7].
• Structure-based amino acid sequence alignments and mutational analysis are used to demonstrate that an RCK domain is also present and is an important component of the gating machinery in eukaryotic large-conductance Ca2+ activated K+ channels [3].
• However, rck/p54 was shown to be very low in the human brain and was not detectable in lumbar muscle and lung tissues, although RCK mRNA is abundantly present in these tissues [8].

Chemical compound and disease context of DDX6

• An antagonist(s) from anaerobic agar cultures of P126 strongly inhibited two closely related strains of propionibacteria, P. acidipropionici P5 and P. jensenii P54, and Lactobacillus bulgaricus NCDO 1489, Lactobacillus delbrueckii subsp. lactis ATCC 4797, Lactococcus cremoris NCDO 799, and Lactococcus lactis subsp. lactis C2 [9].

Biological context of DDX6

• Xp54 belongs to small family of helicases (DDX6) that associate with mRNA molecules encoding proteins required for progress through meiosis [10].
• Identification and chromosome mapping of the mouse homologue of the human gene (DDX6) that encodes a putative RNA helicase of the DEAD box protein family [1].
• Positive mouse genomic and cDNA recombinant clones were obtained by screening mouse B-cell genomic and cDNA libraries with a human DDX6 cDNA probe [1].
• Xp54 and related (DDX6-like) RNA helicases: roles in messenger RNP assembly, translation regulation and RNA degradation [11].
• Translation Repression in Human Cells by MicroRNA-Induced Gene Silencing Requires RCK/p54 [12].

Anatomical context of DDX6

• Here, we substantiate a function of ataxin-2 in such pathways by demonstrating that ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6, a component of P-bodies and stress granules, representing cellular structures of mRNA triage [13].
• The RCK gene was previously cloned at the breakpoint of the t(11;14)(q23;q32) chromosome translocation observed in human B-cell lymphoma cell line RC-K8 [14].
• Thecal and granulosa cells of primordial, primary, and secondary follicles all reacted positively with antibodies to the broad-spectrum keratins OV-TL 12/5 and RCK 102, and to keratins 8 and 18, but not with keratins 4, 7, 13, and 19 [15].
• While both RCK 105 (anti-keratin 7) and OV-TL 12/5 (anti-keratin 5, 7, 14, 19) did not stain on paraffin-embedded sections, the polyclonal control antiserum (pKer) lost immunoreactivity in some cell types (e.g. mucous cells in compound glands, hepatocytes, pancreatic acinar cells, and proximal and distal convoluted tubules of the kidney) [16].
• In addition to this biologically active form of the lymphokine, a strongly immunoreactive protein with a molecular weight of 54 kDa (P54) was found in Jurkat cell lysates [17].

Associations of DDX6 with chemical compounds

• Luminal cells stained with MCA 144, CAM 5.2, RCK 102 and to a lesser degree with PKE [18].
• In formalin-fixed tissue basal cells stained exclusively with Z622, predominantly with PKE and RCK 102, and to lesser degree with MCA 144 and CAM 5 [18].
• In this sense the double antibody method employed by SCK and ICK is clinically more advantageous than is the perchloric acid extraction-zirconyl phosphate gel precipitation method of RCK [19].

Physical interactions of DDX6

• Ataxin-2 Interacts with the DEAD/H-Box RNA Helicase DDX6 and Interferes with P-Bodies and Stress Granules [13].

Other interactions of DDX6

• Depletion of RCK/p54 disrupted P-bodies and dispersed Ago2 throughout the cytoplasm but did not significantly affect siRNA-mediated RNA functions of RISC [12].
• The RCK gene associated with t(11;14) translocation is distinct from the MLL/ALL-1 gene with t(4;11) and t(11;19) translocations [20].
• By pulsed-field gel electrophoresis after NotI digestion, this recombinant clone is on a 96-kilobase fragment, while RCK and PBGD probes are on a more telomeric 690-kilobase NotI fragment [20].

Analytical, diagnostic and therapeutic context of DDX6

• With the use of Northern blot analysis, a 7.5-kb transcript of the RCK gene was shown to be expressed ubiquitously in human and mouse tissues [8].
• Expression of the RCK gene, which is a target gene on 11q23 of the t(11;14) (q23;q32) translocation in the B-cell lymphoma cell line RC-K8, was studied by Northern and Western blot analyses [8].
• Sequence analysis revealed an open reading frame (ORF) predicting a polypeptide of 483 aa showing 97.7% identity to human RCK/p54 [21].
• Monoclonal antibody (RCK 105) directed against keratin 7 was obtained after immunization of BALB/c mice with cytoskeletal preparations from T24 cells and characterized by one- (1D) and two-dimensional (2D) immunoblotting [22].
• RESULTS: Between 1990 and 2001, 146 eviscerations were performed under local anesthesia with monitored anesthesia care by two surgeons (RCK, DRK) as their routine practice pattern [23].

References