ELL2

Summary

Gene Symbol: ELL2
Description: elongation factor for RNA polymerase II 2
Alias: MRCCAT1, RNA polymerase II elongation factor ELL2, ELL-related RNA polymerase II, elongation factor, elongation factor RNA for polymerase II 2, elongation factor, RNA polymerase II, 2, metastatic renal cell carcinoma-associated transcript 1
Species: human
Products:     ELL2

Top Publications

  1. Liu M, Hsu J, Chan C, Li Z, Zhou Q. The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription. Mol Cell. 2012;46:325-34 pubmed publisher
    ..Among all SEC subunits, ELL2 is stoichiometrically limiting and uniquely regulated at the level of protein stability...
  2. He N, Liu M, Hsu J, Xue Y, Chou S, Burlingame A, et al. HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol Cell. 2010;38:428-38 pubmed publisher
    ..scheme, we have identified human transcription factors/coactivators AFF4, ENL, AF9, and elongation factor ELL2 as components of the Tat-P-TEFb complex...
  3. Shilatifard A, Duan D, Haque D, Florence C, Schubach W, Conaway J, et al. ELL2, a new member of an ELL family of RNA polymerase II elongation factors. Proc Natl Acad Sci U S A. 1997;94:3639-43 pubmed
    ..In this report we describe molecular cloning, expression, and characterization of human ELL2, a novel RNA polymerase II elongation factor 49% identical and 66% similar to ELL...
  4. Karn J. The molecular biology of HIV latency: breaking and restoring the Tat-dependent transcriptional circuit. Curr Opin HIV AIDS. 2011;6:4-11 pubmed publisher
    ..Alternatively, new inhibitors that block proviral reactivation could be developed. ..
  5. Li Z, Guo J, Wu Y, Zhou Q. The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation. Nucleic Acids Res. 2013;41:277-87 pubmed publisher
  6. He N, Chan C, Sobhian B, Chou S, Xue Y, Liu M, et al. Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin. Proc Natl Acad Sci U S A. 2011;108:E636-45 pubmed publisher
    The Super Elongation Complex (SEC), containing transcription elongation activators/coactivators P-TEFb, ELL2, AFF4/1, ENL, and AF9, is recruited by HIV-1 Tat and mixed lineage leukemia (MLL) proteins to activate the expression of HIV-1 ..
  7. Chou S, Upton H, Bao K, Schulze Gahmen U, Samelson A, He N, et al. HIV-1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold. Proc Natl Acad Sci U S A. 2013;110:E123-31 pubmed publisher
    ..stimulates viral gene expression by recruiting human transcription elongation complexes containing P-TEFb, AFF4, ELL2, and ENL or AF9 to the viral promoter, but the molecular organization of these complexes remains unknown...
  8. Carew N, Nelson A, Liang Z, Smith S, Milcarek C. Linking Endoplasmic Reticular Stress and Alternative Splicing. Int J Mol Sci. 2018;19: pubmed publisher
    RNA splicing patterns in antibody-secreting cells are shaped by endoplasmic reticulum stress, ELL2 (eleven-nineteen lysine-rich leukemia gene 2) induction, and changes in the levels of snRNAs...
  9. Chung C, Berson A, Kennerdell J, Sartoris A, Unger T, Porta S, et al. Aberrant activation of non-coding RNA targets of transcriptional elongation complexes contributes to TDP-43 toxicity. Nat Commun. 2018;9:4406 pubmed publisher
    ..We further demonstrate an interaction between TDP-43 and human ELL2 by co-immunoprecipitation from human cells...

More Information

Publications39

  1. Liang K, Smith E, Aoi Y, Stoltz K, Katagi H, Woodfin A, et al. Targeting Processive Transcription Elongation via SEC Disruption for MYC-Induced Cancer Therapy. Cell. 2018;175:766-779.e17 pubmed publisher
    ..release of RNA polymerase II (Pol II) with its P-TEFb module and promoting transcriptional processivity with its ELL2 subunit. Malfunction of SEC contributes to multiple human diseases including cancer...
  2. Nelson A, Carew N, Smith S, Milcarek C. RNA Splicing in the Transition from B Cells to Antibody-Secreting Cells: The Influences of ELL2, Small Nuclear RNA, and Endoplasmic Reticulum Stress. J Immunol. 2018;201:3073-3083 pubmed publisher
    In the transition from B cells to Ab-secreting cells (ASCs) many genes are induced, such as ELL2, Irf4, Prdm1, Xbp1, whereas other mRNAs do not change in abundance...
  3. Ali M, Ajore R, Wihlborg A, Niroula A, Swaminathan B, Johnsson E, et al. The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression. Nat Commun. 2018;9:1649 pubmed publisher
    Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM)...
  4. Qi S, Li Z, Schulze Gahmen U, Stjepanovic G, Zhou Q, Hurley J. Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription. Nat Commun. 2017;8:14076 pubmed publisher
    ..Here we report the 2.0-Å resolution crystal structure of the human ELL2 C-terminal domain bound to its 50-residue binding site on AFF4, the ELLBow...
  5. Yu D, Liu R, Yang G, Zhou Q. The PARP1-Siah1 Axis Controls HIV-1 Transcription and Expression of Siah1 Substrates. Cell Rep. 2018;23:3741-3749 pubmed publisher
    ..Because efficient HIV-1 transactivation is known to depend on the ELL2-containing super elongation complex (SEC), we investigated the functional relationship between PARP1 and ELL2-SEC ..
  6. Qiu X, Pascal L, Song Q, Zang Y, Ai J, O Malley K, et al. Physical and Functional Interactions between ELL2 and RB in the Suppression of Prostate Cancer Cell Proliferation, Migration, and Invasion. Neoplasia. 2017;19:207-215 pubmed publisher
    Elongation factor, RNA polymerase II, 2 (ELL2) is expressed and regulated by androgens in the prostate...
  7. Minnich M, Tagoh H, Bönelt P, Axelsson E, Fischer M, Cebolla B, et al. Multifunctional role of the transcription factor Blimp-1 in coordinating plasma cell differentiation. Nat Immunol. 2016;17:331-43 pubmed publisher
    ..expression switch from the membrane-bound form of the immunoglobulin heavy chain to its secreted form by activating Ell2 (which encodes the transcription-elongation factor ELL2)...
  8. Wu Y, Graff R, Passarelli M, Hoffman J, Ziv E, Hoffmann T, et al. Identification of Pleiotropic Cancer Susceptibility Variants from Genome-Wide Association Studies Reveals Functional Characteristics. Cancer Epidemiol Biomarkers Prev. 2018;27:75-85 pubmed publisher
    ..1%) composed of 33 variants (3.3%), including novel pleiotropic variants rs3777204 and rs56219066 located in the ELL2 gene. Relative to single-cancer risk variants, pleiotropic variants were more likely to be in genes (89.0% vs...
  9. Olivares A, Jelcick A, Reinecke J, Leehy B, Haider A, Morrison M, et al. Multimodal Regulation Orchestrates Normal and Complex Disease States in the Retina. Sci Rep. 2017;7:690 pubmed publisher
    ..regulation by miRNA, NHRs, and epigenetic factors of three miRNAs (miR-466, miR1187, and miR-710) and two genes (Ell2 and Entpd1) that are also associated with AMD...
  10. Hodson D, Shaffer A, Xiao W, Wright G, Schmitz R, Phelan J, et al. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2. Proc Natl Acad Sci U S A. 2016;113:E2039-46 pubmed publisher
    ..revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA...
  11. Li Z, Lu H, Zhou Q. A Minor Subset of Super Elongation Complexes Plays a Predominant Role in Reversing HIV-1 Latency. Mol Cell Biol. 2016;36:1194-205 pubmed publisher
    ..Here, we used the CRISPR-Cas9 genome-editing tool to knock out the gene encoding the SEC subunit ELL2, AFF1, or AFF4 in Jurkat/2D10 cells, a well-characterized HIV-1 latency model...
  12. Li Y, Wen H, Xi Y, Tanaka K, Wang H, Peng D, et al. AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation. Cell. 2014;159:558-71 pubmed publisher
    ..Together, our studies identified the evolutionarily conserved YEATS domain as a novel acetyllysine-binding module and established a direct link between histone acetylation and DOT1L-mediated H3K79 methylation in transcription control. ..
  13. Huang Q, Zhang X, Ma Y, Lu G, Xie R, Yang H, et al. Up-regulated microRNA-299 corrected with poor prognosis of glioblastoma multiforme patients by targeting ELL2. Jpn J Clin Oncol. 2017;47:590-596 pubmed publisher
    ..RNA polymerase II elongation factor, ELL2, was identified as a miR-299 direct target...
  14. Li N, Johnson D, Weinhold N, Kimber S, Dobbins S, Mitchell J, et al. Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism. Cell Rep. 2017;20:2556-2564 pubmed publisher
    ..gt; C resides in a predicted enhancer element that physically interacts with the transcription start site of ELL2. The rs6877329-C risk allele is associated with reduced enhancer activity and lowered ELL2 expression...
  15. Swaminathan B, Thorleifsson G, Jöud M, Ali M, Johnsson E, Ajore R, et al. Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma. Nat Commun. 2015;6:7213 pubmed publisher
    ..Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10))...
  16. Mann M, Strobel S, Fleckenstein B, Kress A. The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax. Virology. 2014;464-465:98-110 pubmed publisher
    ..Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells...
  17. Pascal L, Masoodi K, Liu J, Qiu X, Song Q, Wang Y, et al. Conditional deletion of ELL2 induces murine prostate intraepithelial neoplasia. J Endocrinol. 2017;235:123-136 pubmed publisher
    Elongation factor, RNA polymerase II, 2 (ELL2) is an RNA Pol II elongation factor with functional properties similar to ELL that can interact with the prostate tumor suppressor EAF2...
  18. Alexander L, Watters J, Reusch J, Maurin M, Nepon Sixt B, Vrzalikova K, et al. Selective expression of the transcription elongation factor ELL3 in B cells prior to ELL2 drives proliferation and survival. Mol Immunol. 2017;91:8-16 pubmed publisher
    ..This restricted utilization and survival dependence reveal a key step in B cell activation and indicate a potential therapeutic target against B cell lymphoma's with a germinal center origin. ..
  19. Taube R, Peterlin M. Lost in transcription: molecular mechanisms that control HIV latency. Viruses. 2013;5:902-27 pubmed publisher
  20. Simone F, Polak P, Kaberlein J, Luo R, Levitan D, Thirman M. EAF1, a novel ELL-associated factor that is delocalized by expression of the MLL-ELL fusion protein. Blood. 2001;98:201-9 pubmed
    ..In addition, endogenous EAF1 also exhibited the capacity to interact with ELL2. Database comparisons with EAF1 identified a region with a high content of serine, aspartic acid, and glutamic acid ..
  21. Martincic K, Alkan S, Cheatle A, Borghesi L, Milcarek C. Transcription elongation factor ELL2 directs immunoglobulin secretion in plasma cells by stimulating altered RNA processing. Nat Immunol. 2009;10:1102-9 pubmed publisher
    ..The RNA polymerase II transcription elongation factor ELL2, which is induced in plasma cells, enhanced both polyadenylation and exon skipping with the gene encoding the ..
  22. Shen X, Klarić L, Sharapov S, Mangino M, Ning Z, Wu D, et al. Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation. Nat Commun. 2017;8:447 pubmed publisher
    ..cohort, our multi-phenotype method uncovers ten genome-wide significant loci, of which five are novel (IGH, ELL2, HLA-B-C, AZI1, FUT6-FUT3). We convincingly replicate all novel loci via multivariate tests...
  23. Yu X, Ai J, Cai L, Jing Y, Wang D, Dong J, et al. Regulation of tumor suppressor EAF2 polyubiquitination by ELL1 and SIAH2 in prostate cancer cells. Oncotarget. 2016;7:29245-54 pubmed publisher
    ..These findings suggest that SIAH2 is an E3 ligase for EAF2 polyubiquitination and ELL1 can enhance EAF2 level and function by blocking its polyubiquitination. ..
  24. Zang Y, Pascal L, Zhou Y, Qiu X, Wei L, Ai J, et al. ELL2 regulates DNA non-homologous end joining (NHEJ) repair in prostate cancer cells. Cancer Lett. 2018;415:198-207 pubmed publisher
    b>ELL2 is an androgen-responsive gene that is expressed by prostate epithelial cells and is frequently down-regulated in prostate cancer...
  25. Park K, Bayles I, Szlachta McGinn A, Paul J, Boiko J, Santos P, et al. Transcription elongation factor ELL2 drives Ig secretory-specific mRNA production and the unfolded protein response. J Immunol. 2014;193:4663-74 pubmed publisher
    ..The transcription elongation factor eleven nineteen lysine-rich leukemia gene (ELL2) stimulates the processing of the secreted form of the IgH mRNA from the H chain gene...
  26. Simone F, Luo R, Polak P, Kaberlein J, Thirman M. ELL-associated factor 2 (EAF2), a functional homolog of EAF1 with alternative ELL binding properties. Blood. 2003;101:2355-62 pubmed
    ..Thus, MLL-ELL retains an interaction domain for EAF1 but not for EAF2. Taken together, these data suggest that MLL-ELL may disrupt the normal protein-protein interactions of ELL. ..
  27. Alexander L, Watters J, Reusch J, Maurin M, Nepon Sixt B, Vrzalikova K, et al. Data supporting the functional role of Eleven-nineteen Lysine-rich Leukemia 3 (ELL3) in B cell lymphoma cell line cells. Data Brief. 2017;15:222-227 pubmed publisher
    ..the research article entitled "Selective expression of the transcription elongation factor ELL3 in B cells prior to ELL2 drives proliferation and survival" (Alexander et al., 2017) [1]...
  28. Mbonye U, Karn J. Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cure. Virology. 2014;454-455:328-39 pubmed publisher
    ..An in-depth comprehensive understanding of the molecular control of HIV-1 transcription should inform the development of optimal combinatorial reactivation strategies that are intended to purge the latent viral reservoir...
  29. Lu H, Li Z, Xue Y, Schulze Gahmen U, Johnson J, Krogan N, et al. AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation. Proc Natl Acad Sci U S A. 2014;111:E15-24 pubmed publisher
    ..Our data identify AFF1 as a ubiquitous P-TEFb partner and demonstrate that full Tat transactivation requires the complete SEC. ..
  30. Franceschini N, van Rooij F, Prins B, Feitosa M, Karakas M, Eckfeldt J, et al. Discovery and fine mapping of serum protein loci through transethnic meta-analysis. Am J Hum Genet. 2012;91:744-53 pubmed publisher
    ..3, and ELL2, in up to 25,539 European-ancestry and 10,168 Japanese individuals)...