ArticleAmerican journal of blood research2016
DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex.
Article in American journal of blood research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- The KMT2A recombinome of acute leukemias in 2023.Leukemia · 2023Article
- Progress in 7SK ribonucleoprotein structural biology.Frontiers in molecular biosciences · 2023Review
- Discovery of a large-scale, cell-state-responsive allosteric switch in the 7SK RNA using DANCE-MaP.Molecular cell · 2022Article
- MLL-AF4 and a murinized pSer-variant thereof are turning on the nucleolar stress pathway.Cell & bioscience · 2022Article
- Bone Marrow Surveillance of Pediatric Cancer Survivors Identifies Clones that Predict Therapy-Related Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Review
- The Expression and Roles of the Super Elongation Complex in Mouse Cochlear Lgr5+ Progenitor Cells.Frontiers in cellular neuroscience · 2021Article
- Article
- AFF1 inhibits adipogenic differentiation via targeting TGM2 transcription.Cell proliferation · 2020Article
- Structure of the super-elongation complex subunit AFF4 C-terminal homology domain reveals requirements for AFF homo- and heterodimerization.The Journal of biological chemistry · 2019Article
- Unraveling the cellular origin and clinical prognostic markers of infant B-cell acute lymphoblastic leukemia using genome-wide analysis.Haematologica · 2019Article
- Another piece of the puzzle added to understand t(4;11) leukemia better.Haematologica · 2019Article
- Enhanced hemato-endothelial specification during human embryonic differentiation through developmental cooperation betweenHaematologica · 2019Article
- Hexim1, an RNA-controlled protein hub.Transcription · 2018Review
- DEAD-box helicase 6 (DDX6) is a new negative regulator for milk synthesis and proliferation of bovine mammary epithelial cells.In vitro cellular & developmental biology. Animal · 2018Article
- Reconstitution of a functional 7SK snRNP.Nucleic acids research · 2017Article
- Dual mechanisms regulate the nucleocytoplasmic localization of human DDX6.Scientific reports · 2017Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AF4/AFF1 and AF5/AFF4 are both backbones for the assembly of "super elongation complexes" (SECs) that exert 2 distinct functions after the recruitment of P-TEFb from the 7SK snRNP: (1) initiation and elongation of RNA polymerase II gene transcription, and (2) modification of transcribed gene regions by distinct histone methylation patterns. In this study we aimed to investigate one of the initial steps, namely how P-TEFb is transferred from 7SK snRNPs to the SECs. In particular, we were interested in the role of DDX6 that we have recently identified as part of the AF4 complex. DDX6 is an evolutionarily conserved member of the DEAD-box RNA helicase family that is known to control miRNA and mRNA biology (translation, storage and degradation). Overexpressed DDX6 is associated with different cancer types and with c-Myc protein overexpression. We could demonstrate that DDX6 binds to 7SK snRNA and causes the release and transfer of P-TEFb to the AF4/AF4N SEC. DDX6 also binds stably to AF4 and AF4N as demonstrated by GST pull-down and co-immunoprecipitation experiments. As a consequence, overexpression of either AF4/AF4N or DDX6 resulted in a strong increase of mRNA production (5-6 fold), while their simultaneous expression increased the cellular mRNA production by 11-fold. Conversely, the corresponding knockdown of DDX6 decreased mRNA production by 70%. In conclusion, AF4/AF4N and DDX6 represent key molecules for the elongation process of gene transcription and a model will be proposed for the hand-over process of P-TEFb to SECs.
Indexed as
Identifiers
27679741PMC5030405W2528879774What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.