SUPT5H

Summary

Gene Symbol: SUPT5H
Description: SPT5 homolog, DSIF elongation factor subunit
Alias: SPT5, SPT5H, Tat-CT1, transcription elongation factor SPT5, DRB sensitivity-inducing factor 160 kDa subunit, DRB sensitivity-inducing factor large subunit, DSIF large subunit, DSIF p160, Tat-cotransactivator 1 protein, hSPT5, suppressor of Ty 5 homolog
Species: human
Products:     SUPT5H

Top Publications

  1. Palangat M, Renner D, Price D, Landick R. A negative elongation factor for human RNA polymerase II inhibits the anti-arrest transcript-cleavage factor TFIIS. Proc Natl Acad Sci U S A. 2005;102:15036-41 pubmed
    ..Because TFIIS promotes escape from promoter-proximal pauses by stimulating cleavage of back-tracked nascent RNA, TFIIS inhibition may help DSIF/NELF negatively regulate productive transcription. ..
  2. Larochelle S, Batliner J, Gamble M, Barboza N, Kraybill B, Blethrow J, et al. Dichotomous but stringent substrate selection by the dual-function Cdk7 complex revealed by chemical genetics. Nat Struct Mol Biol. 2006;13:55-62 pubmed
    ..known and previously unknown Cdk7 substrates that define two classes: proteins such as Pol II and transcription elongation factor Spt5, recognized efficiently only by the fully activated Cdk7 complex, through sequences surrounding the ..
  3. Larochelle S, Amat R, Glover Cutter K, Sansó M, Zhang C, Allen J, et al. Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II. Nat Struct Mol Biol. 2012;19:1108-15 pubmed publisher
    ..Therefore, cyclin-dependent kinases govern Pol II handoff from initiation to elongation factors and cotranscriptional RNA maturation. ..
  4. Ping Y, Chu C, Cao H, Jacque J, Stevenson M, Rana T. Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5. Retrovirology. 2004;1:46 pubmed
    ..One particular cellular regulatory factor, DSIF subunit human SPT5 (hSpt5), has been implicated in both positively and negatively regulating transcriptional elongation but its role in Tat ..
  5. Kwak Y, Guo J, Prajapati S, Park K, Surabhi R, Miller B, et al. Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties. Mol Cell. 2003;11:1055-66 pubmed
    b>SPT5 and its binding partner SPT4 function in both positively and negatively regulating transcriptional elongation...
  6. Wu Baer F, Lane W, Gaynor R. Role of the human homolog of the yeast transcription factor SPT5 in HIV-1 Tat-activation. J Mol Biol. 1998;277:179-97 pubmed
    ..in the purification of a cellular factor Tat-CT1 which is a human homolog of the yeast transcription factor SPT5. Immunodepletion of Tat-CTl from HeLa extract demonstrated that this factor was involved in transcriptional ..
  7. Wada T, Takagi T, Yamaguchi Y, Watanabe D, Handa H. Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro. EMBO J. 1998;17:7395-403 pubmed
    ..DSIF is a human homolog of the yeast Spt4-Spt5 complex and renders elongation of transcription sensitive to DRB...
  8. Narita T, Yamaguchi Y, Yano K, Sugimoto S, Chanarat S, Wada T, et al. Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex. Mol Cell Biol. 2003;23:1863-73 pubmed
    ..together with DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) sensitivity-inducing factor (DSIF)/human Spt4-Spt5 to cause transcriptional pausing of RNA polymerase II (RNAPII)...
  9. Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, et al. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell. 1999;97:41-51 pubmed
    ..This study reveals a molecular mechanism for DRB action and a regulatory network of positive and negative elongation factors. ..

More Information

Publications93

  1. Yamaguchi Y, Inukai N, Narita T, Wada T, Handa H. Evidence that negative elongation factor represses transcription elongation through binding to a DRB sensitivity-inducing factor/RNA polymerase II complex and RNA. Mol Cell Biol. 2002;22:2918-27 pubmed
    ..NELF) is a human transcription factor complex that cooperates with DRB sensitivity-inducing factor (DSIF)/hSpt4-hSpt5 to repress elongation by RNA polymerase II (RNAPII)...
  2. Ivanov D, Kwak Y, Guo J, Gaynor R. Domains in the SPT5 protein that modulate its transcriptional regulatory properties. Mol Cell Biol. 2000;20:2970-83 pubmed
    b>SPT5 and its binding partner SPT4 regulate transcriptional elongation by RNA polymerase II...
  3. Yamada T, Yamaguchi Y, Inukai N, Okamoto S, Mura T, Handa H. P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation. Mol Cell. 2006;21:227-37 pubmed
    Human DSIF, a heterodimer composed of hSpt4 and hSpt5, plays opposing roles in transcription elongation by RNA polymerase II (RNA Pol II)...
  4. Lavoie S, Albert A, Handa H, Vincent M, Bensaude O. The peptidyl-prolyl isomerase Pin1 interacts with hSpt5 phosphorylated by Cdk9. J Mol Biol. 2001;312:675-85 pubmed
    We identify and characterize several phosphorylated forms of the hSpt5 subunit of the DRB sensitivity-inducing factor (DSIF). A 175-kDa phosphorylated form of hSpt5 is bound to nuclei of interphase HeLa cells...
  5. Fujinaga K, Irwin D, Huang Y, Taube R, Kurosu T, Peterlin B. Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element. Mol Cell Biol. 2004;24:787-95 pubmed
    ..These results better define the transition from abortive to productive transcription and thus replication of HIV. ..
  6. Bourgeois C, Kim Y, Churcher M, West M, Karn J. Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences. Mol Cell Biol. 2002;22:1079-93 pubmed
    ..In addition to TAK, the transcription elongation factor Spt5 is required for the efficient activation of transcriptional elongation by Tat...
  7. Renner D, Yamaguchi Y, Wada T, Handa H, Price D. A highly purified RNA polymerase II elongation control system. J Biol Chem. 2001;276:42601-9 pubmed
    ..We show that TFIIF functionally competes with DSIF and NELF, and this competition is dependent on the relative concentrations of TFIIF and NELF. ..
  8. Kim J, Sharp P. Positive transcription elongation factor B phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase. J Biol Chem. 2001;276:12317-23 pubmed
    ..Here, we show that P-TEFb preferentially phosphorylates hSPT5 as compared with the carboxyl-terminal domain of RNA Pol II in vitro...
  9. Ping Y, Rana T. DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation. J Biol Chem. 2001;276:12951-8 pubmed
    ..These findings reveal a molecular mechanism for the negative and positive regulation of transcriptional elongation at the HIV-1 promoter. ..
  10. Pirngruber J, Shchebet A, Schreiber L, Shema E, Minsky N, Chapman R, et al. CDK9 directs H2B monoubiquitination and controls replication-dependent histone mRNA 3'-end processing. EMBO Rep. 2009;10:894-900 pubmed publisher
    ..Thus, CDK9 acts to integrate phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. ..
  11. Jennings B, Shah S, Yamaguchi Y, Seki M, Phillips R, Handa H, et al. Locus-specific requirements for Spt5 in transcriptional activation and repression in Drosophila. Curr Biol. 2004;14:1680-4 pubmed
    ..We have identified a missense mutation (W049) in the gene encoding the transcriptional elongation factor Spt5 (reviewed in ) which, when homozygous in the maternal germ line, leads to defects in segmental patterning of the ..
  12. Wen Y, Shatkin A. Transcription elongation factor hSPT5 stimulates mRNA capping. Genes Dev. 1999;13:1774-9 pubmed
    RNA polymerase II nascent transcripts are capped during pausing before elongation. Here we report that hSPT5, the human homolog of yeast elongation factor SPT5, interacts directly with the capping enzyme...
  13. Yamaguchi Y, Wada T, Watanabe D, Takagi T, Hasegawa J, Handa H. Structure and function of the human transcription elongation factor DSIF. J Biol Chem. 1999;274:8085-92 pubmed
    ..Here we characterize the structure and function of DSIF p160. p160 is shown to be a ubiquitous nuclear protein that forms a stable complex with p14 and interacts directly ..
  14. Wada T, Takagi T, Yamaguchi Y, Ferdous A, Imai T, Hirose S, et al. DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes Dev. 1998;12:343-56 pubmed
    ..DSIF has been purified and is composed of 160-kD (p160) and 14-kD (p14) subunits. Isolation of a cDNA encoding DSIF p160 shows it to be a homolog of the Saccharomyces cerevisiae transcription factor Spt5...
  15. 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
    ..The ability of Tat to enable two different classes of elongation factors to cooperate and coordinate their actions on the same polymerase enzyme explains why Tat is such a powerful activator of HIV-1 transcription. ..
  16. Kim D, Inukai N, Yamada T, Furuya A, Sato H, Yamaguchi Y, et al. Structure-function analysis of human Spt4: evidence that hSpt4 and hSpt5 exert their roles in transcriptional elongation as parts of the DSIF complex. Genes Cells. 2003;8:371-8 pubmed
    ..Immunodepletion of hSpt5 from HeLa nuclear extracts resulted in the efficient co-depletion of hSpt4...
  17. Garber M, Mayall T, Suess E, Meisenhelder J, Thompson N, Jones K. CDK9 autophosphorylation regulates high-affinity binding of the human immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA. Mol Cell Biol. 2000;20:6958-69 pubmed
    ..Taken together, these results demonstrate that CDK9 phosphorylation is required for high-affinity binding of Tat-P-TEFb to TAR RNA and that the state of P-TEFb phosphorylation may regulate Tat transactivation in vivo. ..
  18. Kim J, Yamaguchi Y, Wada T, Handa H, Sharp P. Tat-SF1 protein associates with RAP30 and human SPT5 proteins. Mol Cell Biol. 1999;19:5960-8 pubmed
    ..The cellular proteins Tat-SF1 and human SPT5 (hSPT5) are required for Tat activation as shown by immunodepletion with specific sera and complementation with ..
  19. Stadelmayer B, Micas G, Gamot A, Martin P, Malirat N, Koval S, et al. Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes. Nat Commun. 2014;5:5531 pubmed publisher
    ..we show that negative elongation factor (NELF) interacts with Integrator complex subunits (INTScom), RNAPII and Spt5. The interaction between NELF and INTScom subunits is RNA and DNA independent...
  20. Maul R, Cao Z, VENKATARAMAN L, Giorgetti C, PRESS J, Denizot Y, et al. Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo-activated cells. J Exp Med. 2014;211:2297-306 pubmed publisher
    ..there is a distinct accumulation of the initiating form of polymerase, along with the transcription cofactor Spt5 and AID, in the V region from germinal center cells, which is totally absent in cultured cells...
  21. Werner F. A nexus for gene expression-molecular mechanisms of Spt5 and NusG in the three domains of life. J Mol Biol. 2012;417:13-27 pubmed publisher
    ..of life-indicative of a common evolutionary descent-this only applies to one RNAP-associated transcription factor-Spt5, also known as NusG in bacteria...
  22. Doamekpor S, Schwer B, Sanchez A, Shuman S, Lima C. Fission yeast RNA triphosphatase reads an Spt5 CTD code. RNA. 2015;21:113-23 pubmed publisher
    ..II (Pol2) transcripts via interactions with the carboxy-terminal domains (CTDs) of Pol2 and transcription elongation factor Spt5. Fission yeast RNA triphosphatase binds to the Spt5 CTD, comprising a tandem repeat of nonapeptide ..
  23. Lawson M, Ma W, Bellecourt M, Artsimovitch I, Martin A, Landick R, et al. Mechanism for the Regulated Control of Bacterial Transcription Termination by a Universal Adaptor Protein. Mol Cell. 2018;71:911-922.e4 pubmed publisher
    NusG/Spt5 proteins are the only transcription factors utilized by all cellular organisms...
  24. Malik S, Barrero M, Jones T. Identification of a regulator of transcription elongation as an accessory factor for the human Mediator coactivator. Proc Natl Acad Sci U S A. 2007;104:6182-7 pubmed
    ..Mass spectrometric analyses identified its two constituent polypeptides as hSpt5 and hSpt4, which also comprise the elongation factor DSIF...
  25. Liu Q, Klingler R, Wimpee B, Dellinger M, KING HEIDEN T, Grzybowski J, et al. Maternal methylmercury from a wild-caught walleye diet induces developmental abnormalities in zebrafish. Reprod Toxicol. 2016;65:272-282 pubmed publisher
    ..affect neuronal and muscular development via dysregulation of genes related to transcriptional regulation (such as supt5h) and cell cycle (such as ccnb1)...
  26. Mbogning J, Pagé V, Burston J, Schwenger E, Fisher R, Schwer B, et al. Functional interaction of Rpb1 and Spt5 C-terminal domains in co-transcriptional histone modification. Nucleic Acids Res. 2015;43:9766-75 pubmed publisher
    ..of this pattern requires phosphorylation of both Rpb1 (the largest RNAPII subunit) and the elongation factor Spt5 on their respective C-terminal domains (CTDs)...
  27. Schwer B, Ghosh A, Sanchez A, Lima C, Shuman S. Genetic and structural analysis of the essential fission yeast RNA polymerase II CTD phosphatase Fcp1. RNA. 2015;21:1135-46 pubmed publisher
    ..Recent studies highlight a second CTD code involving threonine phosphorylation of a repeat motif in transcription elongation factor Spt5. We find that Fcp1 can dephosphorylate Thr1-PO4 of the fission yeast Spt5 CTD nonamer repeat T(1)..
  28. Blythe A, Yazar Klosinski B, Webster M, Chen E, Vandevenne M, Bendak K, et al. The yeast transcription elongation factor Spt4/5 is a sequence-specific RNA binding protein. Protein Sci. 2016;25:1710-21 pubmed publisher
    The heterodimeric transcription elongation factor Spt4/Spt5 (Spt4/5) tightly associates with RNAPII to regulate both transcriptional elongation and co-transcriptional pre-mRNA processing; however, the mechanisms by which Spt4/5 acts are ..
  29. Meyer P, Li S, Zhang M, Yamada K, Takagi Y, Hartzog G, et al. Structures and Functions of the Multiple KOW Domains of Transcription Elongation Factor Spt5. Mol Cell Biol. 2015;35:3354-69 pubmed publisher
    The eukaryotic Spt4-Spt5 heterodimer forms a higher-order complex with RNA polymerase II (and I) to regulate transcription elongation...
  30. Kang J, Mooney R, Nedialkov Y, Saba J, Mishanina T, Artsimovitch I, et al. Structural Basis for Transcript Elongation Control by NusG Family Universal Regulators. Cell. 2018;173:1650-1662.e14 pubmed publisher
    NusG/RfaH/Spt5 transcription elongation factors are the only transcription regulators conserved across all life...
  31. Zuber P, Hahn L, Reinl A, Schweimer K, Knauer S, Gottesman M, et al. Structure and nucleic acid binding properties of KOW domains 4 and 6-7 of human transcription elongation factor DSIF. Sci Rep. 2018;8:11660 pubmed publisher
    ..DSIF is a heterodimer, consisting of Spt4 and Spt5 that interacts with RNA polymerase II (RNAP II)...
  32. Methot S, Litzler L, Subramani P, Eranki A, Fifield H, Patenaude A, et al. A licensing step links AID to transcription elongation for mutagenesis in B cells. Nat Commun. 2018;9:1248 pubmed publisher
    ..Both wt AID and mutants with single amino acid replacements in this domain broadly associate with Spt5 and chromatin and occupy the promoter of AID target genes...
  33. Qiu Y, Gilmour D. Identification of Regions in the Spt5 Subunit of DRB Sensitivity-inducing Factor (DSIF) That Are Involved in Promoter-proximal Pausing. J Biol Chem. 2017;292:5555-5570 pubmed publisher
    ..The mechanism of how DSIF establishes pausing is not known. We constructed Spt5 mutant forms of DSIF and tested their capacity to restore promoter-proximal pausing to DSIF-depleted Drosophila
  34. Tastemel M, Gogate A, Malladi V, Nguyen K, Mitchell C, Banaszynski L, et al. Transcription pausing regulates mouse embryonic stem cell differentiation. Stem Cell Res. 2017;25:250-255 pubmed publisher
    ..in regulating ESC pluripotency, we have generated mouse ESCs carrying a mutation in the pause-inducing factor SPT5. Genomic studies reveal genome-wide reduction of paused Pol II caused by mutant SPT5 and further identify a tight ..
  35. Amir Zilberstein L, Dikstein R. Interplay between E-box and NF-kappaB in regulation of A20 gene by DRB sensitivity-inducing factor (DSIF). J Biol Chem. 2008;283:1317-23 pubmed
    ..These findings reveal a dynamic regulation of DSIF involving either E-box or NF-kappaB depending on the physiological circumstances. ..
  36. Crickard J, Fu J, Reese J. Biochemical Analysis of Yeast Suppressor of Ty 4/5 (Spt4/5) Reveals the Importance of Nucleic Acid Interactions in the Prevention of RNA Polymerase II Arrest. J Biol Chem. 2016;291:9853-70 pubmed publisher
    ..NusG/Spt5 is the only elongation factor conserved in all domains of life...
  37. Lu X, Zhu X, Li Y, Liu M, Yu B, Wang Y, et al. Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II. Nucleic Acids Res. 2016;44:6853-67 pubmed publisher
    ..Upon stimulation, Brd4 recruits P-TEFb to Spt5/DSIF via a recruitment pathway consisting of Med1, Med23 and Tat-SF1, whereas SEC recruits P-TEFb to NELF-A and ..
  38. Lu C, Tian Y, Wang S, Su Y, Mao T, Huang T, et al. Phosphorylation of SPT5 by CDKD;2 Is Required for VIP5 Recruitment and Normal Flowering in Arabidopsis thaliana. Plant Cell. 2017;29:277-291 pubmed publisher
    The elongation factor suppressor of Ty 5 homolog (Spt5) is a regulator of transcription and histone methylation...
  39. Booth G, Parua P, Sansó M, Fisher R, Lis J. Cdk9 regulates a promoter-proximal checkpoint to modulate RNA polymerase II elongation rate in fission yeast. Nat Commun. 2018;9:543 pubmed publisher
    ..Within a minute of Cdk9 inhibition, phosphorylation of Pol II-associated factor, Spt5 is undetectable...
  40. Diamant G, Bahat A, Dikstein R. The elongation factor Spt5 facilitates transcription initiation for rapid induction of inflammatory-response genes. Nat Commun. 2016;7:11547 pubmed publisher
    ..Here we followed the kinetics of primary transcript accumulation after NF-?B activation when the elongation factor Spt5 is knocked down...
  41. Williams A, Maman Y, Alinikula J, Schatz D. Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells. PLoS ONE. 2016;11:e0149146 pubmed publisher
    ..In contrast, association of Spt5, an RNA polymerase II (Pol II) and AID binding factor, was strongly reduced at the target gene body relative to the ..
  42. Wada T, Orphanides G, Hasegawa J, Kim D, Shima D, Yamaguchi Y, et al. FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Mol Cell. 2000;5:1067-72 pubmed
    ..In addition, this study reveals functional differences between P-TEFb and TFIIH in the regulation of transcription. ..
  43. Fox H, Dembowski J, DeLuca N. A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts. MBio. 2017;8: pubmed publisher
    ..ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes...
  44. Li S. Transcription coupled nucleotide excision repair in the yeast Saccharomyces cerevisiae: The ambiguous role of Rad26. DNA Repair (Amst). 2015;36:43-8 pubmed publisher
    ..absence of Rpb4, another nonessential subunit of RNAP II, or a number of transcription elongation factors (Spt4, Spt5 and the RNAP II associated factor complex)...
  45. Baejen C, Andreani J, Torkler P, Battaglia S, Schwalb B, Lidschreiber M, et al. Genome-wide Analysis of RNA Polymerase II Termination at Protein-Coding Genes. Mol Cell. 2017;66:38-49.e6 pubmed publisher
    ..We find that the 3'-transition globally requires the Pol II elongation factor Spt5 and factors involved in the recognition of the polyadenylation (pA) site and in endonucleolytic RNA cleavage...
  46. Martínez Fernández V, Garrido Godino A, Mirón García M, Begley V, Fernández Pévida A, de la Cruz J, et al. Rpb5 modulates the RNA polymerase II transition from initiation to elongation by influencing Spt5 association and backtracking. Biochim Biophys Acta Gene Regul Mech. 2018;1861:1-13 pubmed publisher
    ..and is linked to differences in the phosphorylation state of the RNA polymerase II and reduced recruitment of Spt5 to transcribe chromatin, thus influencing its anti-backtracking activity...
  47. Shetty A, Kallgren S, Demel C, Maier K, Spatt D, Alver B, et al. Spt5 Plays Vital Roles in the Control of Sense and Antisense Transcription Elongation. Mol Cell. 2017;66:77-88.e5 pubmed publisher
    b>Spt5 is an essential and conserved factor that functions in transcription and co-transcriptional processes. However, many aspects of the requirement for Spt5 in transcription are poorly understood...
  48. Köllen K, Dietz L, Bies Etheve N, Lagrange T, Grasser M, Grasser K. The zinc-finger protein SPT4 interacts with SPT5L/KTF1 and modulates transcriptional silencing in Arabidopsis. FEBS Lett. 2015;589:3254-7 pubmed publisher
    The Arabidopsis multidomain protein SPT5L/KTF1 (which has similarity to the transcript elongation factor SPT5) associates with RNA polymerase V (RNAPV) and is an accessory factor in RNA-directed DNA methylation...
  49. Yakhnin A, Murakami K, Babitzke P. NusG Is a Sequence-specific RNA Polymerase Pause Factor That Binds to the Non-template DNA within the Paused Transcription Bubble. J Biol Chem. 2016;291:5299-308 pubmed publisher
    NusG, referred to as Spt5 in archaeal and eukaryotic organisms, is the only transcription factor conserved in all three domains of life...
  50. Mousseau G, Mediouni S, Valente S. Targeting HIV transcription: the quest for a functional cure. Curr Top Microbiol Immunol. 2015;389:121-45 pubmed publisher
    ..Finally, we discuss the impact of extracellular Tat in HIV-associated neurocognitive disorders and cancers. ..
  51. Komori T, Inukai N, Yamada T, Yamaguchi Y, Handa H. Role of human transcription elongation factor DSIF in the suppression of senescence and apoptosis. Genes Cells. 2009;14:343-54 pubmed publisher
    ..conserved, ubiquitously expressed, heterodimeric transcription elongation factor composed of two subunits, Spt4 and Spt5. Previous biochemical studies have shown that DSIF positively and negatively regulates RNA polymerase II elongation ..
  52. Bernecky C, Plitzko J, Cramer P. Structure of a transcribing RNA polymerase II-DSIF complex reveals a multidentate DNA-RNA clamp. Nat Struct Mol Biol. 2017;24:809-815 pubmed publisher
    ..The mobile C-terminal region of DSIF is located near exiting RNA, where it can recruit factors for RNA processing. The structure provides insight into the roles of DSIF during mRNA synthesis. ..
  53. McKnight N, Jefferies H, Alemu E, Saunders R, Howell M, Johansen T, et al. Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC. EMBO J. 2012;31:1931-46 pubmed publisher
    ..The identification of these novel regulatory proteins with diverse functions in autophagy contributes towards a fuller understanding of autophagosome formation. ..
  54. Zhao Z, Tang K, Muylaert I, Samuelsson T, Elias P. CDK9 and SPT5 proteins are specifically required for expression of herpes simplex virus 1 replication-dependent late genes. J Biol Chem. 2017;292:15489-15500 pubmed publisher
    ..In addition, we show that siRNA-mediated knockdown of the transcription factor SPT5, but not NELF-E, also gives rise to a specific inhibition of HSV-1 late gene expression...
  55. Pereira A, Paro R. Pho dynamically interacts with Spt5 to facilitate transcriptional switches at the hsp70 locus. Epigenetics Chromatin. 2017;10:57 pubmed publisher
    ..We found that Pleiohomeotic (Pho), a DNA-binding PcG member, dynamically interacts with Spt5, an elongation factor...
  56. Stachora A, Schäfer R, Pohlmeier M, Maier G, Ponstingl H. Human Supt5h protein, a putative modulator of chromatin structure, is reversibly phosphorylated in mitosis. FEBS Lett. 1997;409:74-8 pubmed
    ..One of them, with the consensus sequence P-T/S-P-S-P-Q/A-S/G-Y, is similar to the C-terminal domain in the largest subunit of RNA polymerase II. ..
  57. Hogenbirk M, Heideman M, de Rink I, Velds A, Kerkhoven R, Wessels L, et al. Defining chromosomal translocation risks in cancer. Proc Natl Acad Sci U S A. 2016;113:E3649-56 pubmed publisher
    ..recent reports, we demonstrate that chromosomal translocation risk is causally unrelated to promoter stalling (Spt5), transcriptional activity, or off-targeting activity of the activation-induced cytidine deaminase...
  58. Resto M, Kim B, Fernandez A, Abraham B, Zhao K, Lewis B. O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1?. J Biol Chem. 2016;291:22703-22713 pubmed
    ..Furthermore, OGA is physically associated with the known RNA polymerase II (pol II) pausing/elongation factors SPT5 and TRIM28-KAP1-TIF1?, and a purified OGA-SPT5-TIF1? complex has elongation properties...
  59. Chiang P, Fogel E, Jackson C, Lieuallen K, Lennon G, Qu X, et al. Isolation, sequencing, and mapping of the human homologue of the yeast transcription factor, SPT5. Genomics. 1996;38:421-4 pubmed
    We isolated the human homologue, SUPT5H, of the yeast transcription factor, SPT5. The human homologue is 1088 aa long compared to 1063 aa for the yeast gene. SUPT5H maps to 19q13, near the ryanodine receptor...
  60. Amir Zilberstein L, Ainbinder E, Toube L, Yamaguchi Y, Handa H, Dikstein R. Differential regulation of NF-kappaB by elongation factors is determined by core promoter type. Mol Cell Biol. 2007;27:5246-59 pubmed
    ..The results highlight a regulatory link between the initiation and the elongation phases of the transcription reaction and broaden our comprehension of the NF-kappaB pathway. ..
  61. Chen H, Contreras X, Yamaguchi Y, Handa H, Peterlin B, Guo S. Repression of RNA polymerase II elongation in vivo is critically dependent on the C-terminus of Spt5. PLoS ONE. 2009;4:e6918 pubmed publisher
    ..b>Spt5, the large subunit of the DRB sensitivity-inducing factor (DSIF), represses or activates RNAPII elongation in vitro...
  62. Taube R, Peterlin M. Lost in transcription: molecular mechanisms that control HIV latency. Viruses. 2013;5:902-27 pubmed publisher
  63. Diamant G, Amir Zilberstein L, Yamaguchi Y, Handa H, Dikstein R. DSIF restricts NF-?B signaling by coordinating elongation with mRNA processing of negative feedback genes. Cell Rep. 2012;2:722-31 pubmed publisher
    ..Interestingly, the Spt5 C-terminal repeat (CTR) domain involved in elongation stimulation through P-TEFb is dispensable for I?B? and A20 ..
  64. Kang H, Lieberman P. Mechanism of glycyrrhizic acid inhibition of Kaposi's sarcoma-associated herpesvirus: disruption of CTCF-cohesin-mediated RNA polymerase II pausing and sister chromatid cohesion. J Virol. 2011;85:11159-69 pubmed publisher
    ..GA altered the enrichment of the RNAPII pausing complex, along with pausing factors SPT5 and NELF-A, at the intragenic CTCF-cohesin binding sites...
  65. Michels A, Fraldi A, Li Q, Adamson T, Bonnet F, Nguyen V, et al. Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor. EMBO J. 2004;23:2608-19 pubmed
    ..We propose that the RNA-binding domain of HEXIM1 mediates its association with 7SK and that P-TEFb then enters the complex through association with HEXIM1. ..
  66. Zhou M, Deng L, Lacoste V, Park H, Pumfery A, Kashanchi F, et al. Coordination of transcription factor phosphorylation and histone methylation by the P-TEFb kinase during human immunodeficiency virus type 1 transcription. J Virol. 2004;78:13522-33 pubmed
    ..the RNA polymerase II (RNAP II) carboxyl-terminal domain (CTD) and the transcription elongation factors SPT5 and Tat-SF1 in a Tat/TAR-dependent manner...
  67. Wenzel S, Martins B, Rosch P, Wohrl B. Crystal structure of the human transcription elongation factor DSIF hSpt4 subunit in complex with the hSpt5 dimerization interface. Biochem J. 2009;425:373-80 pubmed publisher
    ..sensitivity-inducing factor] is composed of two subunits, hSpt4 and hSpt5, which are homologous to the yeast factors Spt4 and Spt5...
  68. Diamant G, Eisenbaum T, Leshkowitz D, Dikstein R. Analysis of Subcellular RNA Fractions Revealed a Transcription-Independent Effect of Tumor Necrosis Factor Alpha on Splicing, Mediated by Spt5. Mol Cell Biol. 2016;36:1342-53 pubmed publisher
    ..Here, we examined the global effects of the elongation factor Spt5 on nascent and mature mRNAs of TNF-α-induced cells using chromatin and cytosolic subcellular fractions...
  69. Antosz W, Pfab A, Ehrnsberger H, Holzinger P, Köllen K, Mortensen S, et al. The Composition of the Arabidopsis RNA Polymerase II Transcript Elongation Complex Reveals the Interplay between Elongation and mRNA Processing Factors. Plant Cell. 2017;29:854-870 pubmed publisher
    ..with affinity purification and mass spectrometry, we demonstrate that in Arabidopsis thaliana, the TEFs SPT4/SPT5, SPT6, FACT, PAF1-C, and TFIIS copurified with each other and with elongating RNAPII, while P-TEFb was not among ..
  70. Endoh M, Zhu W, Hasegawa J, Watanabe H, Kim D, Aida M, et al. Human Spt6 stimulates transcription elongation by RNA polymerase II in vitro. Mol Cell Biol. 2004;24:3324-36 pubmed
    ..elongation both individually and in concert with DRB sensitivity-inducing factor (DSIF), comprising human Spt5 and human Spt4. We also provide evidence showing that hSpt6 interacts with RNAPII and DSIF in human cells...
  71. Wier A, Mayekar M, Heroux A, Arndt K, VanDemark A. Structural basis for Spt5-mediated recruitment of the Paf1 complex to chromatin. Proc Natl Acad Sci U S A. 2013;110:17290-5 pubmed publisher
    ..of the Rtf1 subunit mediates Paf1C recruitment to genes by binding a repeating domain within the elongation factor Spt5 (suppressor of Ty)...
  72. White E, Schlackow M, Kamieniarz Gdula K, Proudfoot N, Gullerova M. Human nuclear Dicer restricts the deleterious accumulation of endogenous double-stranded RNA. Nat Struct Mol Biol. 2014;21:552-9 pubmed publisher
    ..Our results suggest that Pol II-associated Dicer restricts endogenous dsRNA formation from overlapping noncoding-RNA transcription units. Failure to do so has catastrophic effects on cell function. ..
  73. Parada C, Roeder R. A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription. EMBO J. 1999;18:3688-701 pubmed
    ..Remarkably, Tat-SF contains the previously identified Tat cofactors Tat-SF1, P-TEFb and hSPT5/Tat-CT1, in addition to RNA Pol II and other unidentified polypeptides, but none of the SRB/MED proteins or other ..
  74. Bernecky C, Herzog F, Baumeister W, Plitzko J, Cramer P. Structure of transcribing mammalian RNA polymerase II. Nature. 2016;529:551-4 pubmed publisher
    ..This position of upstream DNA allows for binding of the general transcription elongation factor DSIF (SPT4-SPT5) that we localize over the active centre cleft in a conserved position on the clamp domain of Pol II...
  75. Yik J, Chen R, Nishimura R, Jennings J, Link A, Zhou Q. Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Mol Cell. 2003;12:971-82 pubmed
  76. Mo X, Dynan W. Subnuclear localization of Ku protein: functional association with RNA polymerase II elongation sites. Mol Cell Biol. 2002;22:8088-99 pubmed
    ..Tethering of double-strand break repair proteins to defined subnuclear structures may also be advantageous in maintenance of genome stability. ..
  77. Mandal S, Chu C, Wada T, Handa H, Shatkin A, Reinberg D. Functional interactions of RNA-capping enzyme with factors that positively and negatively regulate promoter escape by RNA polymerase II. Proc Natl Acad Sci U S A. 2004;101:7572-7 pubmed
    ..This functional interaction between CE and the negative elongation factor documents a dynamic role of CE in promoter clearance beyond its catalytic activities. ..
  78. Chen Y, Yamaguchi Y, Tsugeno Y, Yamamoto J, Yamada T, Nakamura M, et al. DSIF, the Paf1 complex, and Tat-SF1 have nonredundant, cooperative roles in RNA polymerase II elongation. Genes Dev. 2009;23:2765-77 pubmed publisher
    Transcription elongation factor DSIF/Spt4-Spt5 is capable of promoting and inhibiting RNA polymerase II elongation and is involved in the expression of various genes...
  79. Ehara H, Yokoyama T, Shigematsu H, Yokoyama S, Shirouzu M, Sekine S. Structure of the complete elongation complex of RNA polymerase II with basal factors. Science. 2017;357:921-924 pubmed publisher
    ..Spt4/5 (the Spt4/Spt5 complex) and Elf1 modify a wide area of the Pol II surface...
  80. Karn J, Stoltzfus C. Transcriptional and posttranscriptional regulation of HIV-1 gene expression. Cold Spring Harb Perspect Med. 2012;2:a006916 pubmed publisher
    ..In cells that are not fully activated, limiting levels of Tat and Rev act as potent blocks to premature virus production. ..
  81. Jiang J, Cleveland D. Bidirectional Transcriptional Inhibition as Therapy for ALS/FTD Caused by Repeat Expansion in C9orf72. Neuron. 2016;92:1160-1163 pubmed publisher
    ..Kramer et al. (2016) report in Science that targeted reduction in the transcription elongation factor SUPT4H1/SUPT5H reduces both sense and antisense repeat-containing RNAs and their associated neurodegeneration.
  82. Sanchez A, De Vivo A, Uprety N, Kim J, Stevens S, Kee Y. BMI1-UBR5 axis regulates transcriptional repression at damaged chromatin. Proc Natl Acad Sci U S A. 2016;113:11243-11248 pubmed
    ..Altogether, these results suggest that BMI1 and UBR5 repress the polymerase II (Pol II)-mediated transcription at damaged sites, by negatively regulating the FACT-dependent Pol II elongation. ..
  83. Chen R, Zhu J, Dong Y, He C, Hu X. Suppressor of Ty homolog-5, a novel tumor-specific human telomerase reverse transcriptase promoter-binding protein and activator in colon cancer cells. Oncotarget. 2015;6:32841-55 pubmed publisher
    ..In the present study, suppressor of Ty homolog-5 (SPT5), a protein encoded by the SUPT5H gene, was identified as a novel tumor-specific hTERT promoter-binding protein and activator in colon cancer cells...
  84. Cui P, Jin H, Vutukuru M, Kaplan C. Relationships Between RNA Polymerase II Activity and Spt Elongation Factors to Spt- Phenotype and Growth in Saccharomyces cerevisiae. G3 (Bethesda). 2016;6:2489-504 pubmed publisher
    ..cooperating and antagonistic genetic interactions between Pol II alleles and alleles of elongation factors SPT4, SPT5, and SPT6 We find that cryptic transcription at FLO8 and STE11 is distinct from that at lys2-128?, though all show ..