Genomes and Genes
Gene Symbol: POLR2K
Description: RNA polymerase II subunit K
Alias: ABC10-alpha, RPABC4, RPB10alpha, RPB12, RPB7.0, hRPB7.0, hsRPB10a, DNA-directed RNA polymerases I, II, and III subunit RPABC4, DNA directed RNA polymerases I, II, and III 7.0 kda polypeptide, DNA-directed RNA polymerase II subunit K, RNA polymerase II 7.0 kDa subunit, RNA polymerases I, II, and III subunit ABC4, polymerase (RNA) II (DNA directed) polypeptide K, 7.0kDa, polymerase (RNA) II subunit K
- Herrmann C, Rice A. Lentivirus Tat proteins specifically associate with a cellular protein kinase, TAK, that hyperphosphorylates the carboxyl-terminal domain of the large subunit of RNA polymerase II: candidate for a Tat cofactor. J Virol. 1995;69:1612-20 pubmed..Taken together, these results imply that TAK is a very promising candidate for a cellular factor that mediates Tat transactivation. ..
- Kim Y, Bourgeois C, Isel C, Churcher M, Karn J. Phosphorylation of the RNA polymerase II carboxyl-terminal domain by CDK9 is directly responsible for human immunodeficiency virus type 1 Tat-activated transcriptional elongation. Mol Cell Biol. 2002;22:4622-37 pubmed..We conclude that phosphorylation of the RNA polymerase II CTD by CDK9 enhances transcription elongation directly. ..
- 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..This novel biochemical function of Spt5 is analogous to the function of NusG, an elongation factor found in Escherichia coli that enhances RNA polymerase stability on templates and shows sequence similarity to Spt5. ..
- 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. ..
- ..Several approaches are under exploration for reactivating latent virus with the hope that this will allow elimination of the latent reservoir. ..
- Kato H, Sumimoto H, Pognonec P, Chen C, Rosen C, Roeder R. HIV-1 Tat acts as a processivity factor in vitro in conjunction with cellular elongation factors. Genes Dev. 1992;6:655-66 pubmed..We propose the hypothesis that Tat acts as a processivity factor on RNA polymerase II in an analogous manner to TFIIF. ..
- Hogan T, Nonnemacher M, Krebs F, Henderson A, Wigdahl B. HIV-1 Vpr binding to HIV-1 LTR C/EBP cis-acting elements and adjacent regions is sequence-specific. Biomed Pharmacother. 2003;57:41-8 pubmed..These studies suggest that Vpr may regulate the interaction of members of the C/EBP transcription factor family with the viral LTR. ..
- Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva F, Li M, et al. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 2004;6:731-40 pubmed..Furthermore, activation of SMYD3 may be a key factor in human carcinogenesis. ..
- Zhao W, Liu Y, Timani K, He J. Tip110 protein binds to unphosphorylated RNA polymerase II and promotes its phosphorylation and HIV-1 long terminal repeat transcription. J Biol Chem. 2014;289:190-202 pubmed publisher..Taken together, these findings have provided additional and mechanistic evidence to support Tip110 function in HIV-1 transcription. ..
- Nekhai S, Zhou M, Fernandez A, Lane W, Lamb N, Brady J, et al. HIV-1 Tat-associated RNA polymerase C-terminal domain kinase, CDK2, phosphorylates CDK7 and stimulates Tat-mediated transcription. Biochem J. 2002;364:649-57 pubmed..They are also consistent with the observed cell-cycle-specific induction of viral gene transactivation. ..
- Sawaya B, Khalili K, Gordon J, Taube R, Amini S. Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. J Biol Chem. 2000;275:35209-14 pubmed..Moreover identification of R73S mutant of Vpr provides a new therapeutic avenue for controlling HIV-1 gene transcription and replication in the infected cells. ..
- Southgate C, Zapp M, Green M. Activation of transcription by HIV-1 Tat protein tethered to nascent RNA through another protein. Nature. 1990;345:640-2 pubmed..Our results further suggest that cellular proteins that bind specifically to TAR RNA or TAR DNA may not be essential for Tat-responsiveness. ..
- Kiernan R, Vanhulle C, Schiltz L, Adam E, Xiao H, Maudoux F, et al. HIV-1 tat transcriptional activity is regulated by acetylation. EMBO J. 1999;18:6106-18 pubmed..These data suggest that acetylation of Tat regulates two discrete and functionally critical steps in transcription, binding to an RNAP II CTD-kinase and release of Tat from TAR RNA. ..
- HU W, Hughes S. HIV-1 reverse transcription. Cold Spring Harb Perspect Med. 2012;2: pubmed publisher..In keeping with the theme of the collection, the emphasis is on HIV-1 and HIV-1 RT. ..
- Hirschler Laszkiewicz I, Cavanaugh A, Mirza A, Lun M, Hu Q, Smink T, et al. Rrn3 becomes inactivated in the process of ribosomal DNA transcription. J Biol Chem. 2003;278:18953-9 pubmed..Our results indicate that Rrn3 functions stoichiometrically in rDNA transcription and that its ability to associate with RNA polymerase I is lost upon transcription. ..
- Deng L, Ammosova T, Pumfery A, Kashanchi F, Nekhai S. HIV-1 Tat interaction with RNA polymerase II C-terminal domain (CTD) and a dynamic association with CDK2 induce CTD phosphorylation and transcription from HIV-1 promoter. J Biol Chem. 2002;277:33922-9 pubmed..We suggest that CDK2 is part of a transcription complex that is required for Tat-dependent transcription and that interaction of Tat with CTD and a dynamic association of Tat with CDK2/cyclin E stimulated CTD phosphorylation by CDK2. ..
- Howe K. RNA polymerase II conducts a symphony of pre-mRNA processing activities. Biochim Biophys Acta. 2002;1577:308-24 pubmed
- Okamoto H, Sheline C, Corden J, Jones K, Peterlin B. Trans-activation by human immunodeficiency virus Tat protein requires the C-terminal domain of RNA polymerase II. Proc Natl Acad Sci U S A. 1996;93:11575-9 pubmed..These results suggest that effects of Tat on the processivity of RNA polymerase II require proteins that are associated with the CTD and may result in the phosphorylation of the CTD. ..
- Bokar J, Shambaugh M, Polayes D, Matera A, Rottman F. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA. 1997;3:1233-47 pubmed..MT-A70 also contains a long region of homology to the yeast protein SPO8, which is involved in induction of sporulation by an unknown mechanism. ..
- Ramanathan Y, Reza S, Young T, Mathews M, PE ERY T. Human and rodent transcription elongation factor P-TEFb: interactions with human immunodeficiency virus type 1 tat and carboxy-terminal domain substrate. J Virol. 1999;73:5448-58 pubmed..We suggest a model in which Tat first interacts with P-TEFb to form the TAK complex that engages with TAR RNA and the elongating transcription complex, resulting in hyperphosphorylation of the CTD on serine 5 residues. ..
- Parada C, Roeder R. A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription. EMBO J. 1999;18:3688-701 pubmed..Our results indicate that Tat-SF is a Tat cofactor-containing RNA Pol II complex whose recruitment to the promoter provides elongation factors important for Tat-enhanced HIV-1 transcription following TAR RNA synthesis. ..
- Nekhai S, Shukla R, Kumar A. A human primary T-lymphocyte-derived human immunodeficiency virus type 1 Tat-associated kinase phosphorylates the C-terminal domain of RNA polymerase II and induces CAK activity. J Virol. 1997;71:7436-41 pubmed..Importantly, the Tat-associated kinase markedly induced CAK. We suggest that the mechanism of Tat-mediated processive transcription of the HIV-1 promoter includes a Tat-associated CAK activator. ..
- Okamoto T. [Positive and negative regulation of transcription from HIV provirus]. Uirusu. 2011;61:81-9 pubmed..HIV is unique in that it contains virus-specific transcriptional activator called Tat. ..
- Shpakovski G, Acker J, Wintzerith M, Lacroix J, Thuriaux P, Vigneron M. Four subunits that are shared by the three classes of RNA polymerase are functionally interchangeable between Homo sapiens and Saccharomyces cerevisiae. Mol Cell Biol. 1995;15:4702-10 pubmed..6, hRPB17, and hRPB14.4 (referred to as Hs10 alpha, Hs10 beta, Hs8, and Hs6, respectively), homologous to the ABC10 alpha, ABC10 beta, ABC14...
- Kino T, Gragerov A, Kopp J, Stauber R, Pavlakis G, Chrousos G. The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor. J Exp Med. 1999;189:51-62 pubmed..The glucocorticoid coactivator activity of Vpr may contribute to increased tissue glucocorticoid sensitivity in the absence of hypercortisolism and to the pathogenesis of AIDS. ..
- Jung C, Choi S, Im D. The NS5A protein of hepatitis C virus represses gene expression of hRPB10alpha, a common subunit of host RNA polymerases, through interferon regulatory factor-1 binding site. Virus Res. 2007;129:155-65 pubmed..The results suggest that NS5A may partly modulate host cell transcription by the down-regulation of hRPB10alpha. ..
- Wu Baer F, Sigman D, Gaynor R. Specific binding of RNA polymerase II to the human immunodeficiency virus trans-activating region RNA is regulated by cellular cofactors and Tat. Proc Natl Acad Sci U S A. 1995;92:7153-7 pubmed..These results suggest that Tat may function to alter RNA polymerase II, which is paused due to its binding to HIV-1 TAR RNA with resultant stimulation of its transcriptional elongation properties. ..
- Zhou M, Kashanchi F, Jiang H, Ge H, Brady J. Phosphorylation of the RAP74 subunit of TFIIF correlates with Tat-activated transcription of the HIV-1 long terminal repeat. Virology. 2000;268:452-60 pubmed..Of importance, the exogenous RAP74 was rapidly phosphorylated in the presence of Tat. These results suggest that RAP74 phosphorylation is one important step, of several, in the Tat transactivation cascade. ..
- Xiao H, Palhan V, Yang Y, Roeder R. TIP30 has an intrinsic kinase activity required for up-regulation of a subset of apoptotic genes. EMBO J. 2000;19:956-63 pubmed..These data demonstrate a molecular mechanism for TIP30/CC3 function and suggest a novel pathway for regulating apoptosis. ..
- Schaller S, Grandemange S, Shpakovski G, Golemis E, Kedinger C, Vigneron M. Interactions between the full complement of human RNA polymerase II subunits. FEBS Lett. 1999;461:253-7 pubmed..Finally, complementation experiments in yeast indicated that hRPB4 expression efficiently cured both heat and cold-sensitivity of RPB4-lacking strains, supporting the existence of conserved functional subunit interactions. ..
- ..Now, Pagans and colleagues report that the lysine methyltransferase Set7/9-KMT7 associates with Tat to stimulate RNA polymerase II elongation of the integrated provirus. Set7/9-KMT7 also methylates Tat, and this enhances Tat function. ..
- Yankulov K, Bentley D. Transcriptional control: Tat cofactors and transcriptional elongation. Curr Biol. 1998;8:R447-9 pubmed..Recent results show that two cellular cyclin-dependent kinases, which phosphorylate the carboxy-terminal domain of the RNA polymerase II large subunit, contact Tat and contribute to the control of transcriptional elongation. ..
- Cujec T, Okamoto H, Fujinaga K, Meyer J, Chamberlin H, Morgan D, et al. The HIV transactivator TAT binds to the CDK-activating kinase and activates the phosphorylation of the carboxy-terminal domain of RNA polymerase II. Genes Dev. 1997;11:2645-57 pubmed..Our data identify a cellular protein that interacts with the activation domain of Tat, demonstrate that this interaction is critical for the function of Tat, and provide a mechanism by which Tat increases the processivity of Pol II. ..
- Yang X, Herrmann C, Rice A. The human immunodeficiency virus Tat proteins specifically associate with TAK in vivo and require the carboxyl-terminal domain of RNA polymerase II for function. J Virol. 1996;70:4576-84 pubmed..These observations strengthen the proposal that the mechanism of action of Tat involves the recruitment or activation of TAK, resulting in activated transcription through phosphorylation of the CTD. ..
- Kontorovich T, Levy A, Korostishevsky M, Nir U, Friedman E. Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women. Int J Cancer. 2010;127:589-97 pubmed publisher..This study provides preliminary evidence for another regulatory level of penetrance of deleterious mutations in cancer predisposition genes. ..
- Cramer P, Bushnell D, Fu J, Gnatt A, Maier Davis B, Thompson N, et al. Architecture of RNA polymerase II and implications for the transcription mechanism. Science. 2000;288:640-9 pubmed..A pore in the protein complex beneath the active center may allow entry of substrates for polymerization and exit of the transcript during proofreading and passage through pause sites in the DNA. ..
- García Martínez L, Mavankal G, Neveu J, Lane W, Ivanov D, Gaynor R. Purification of a Tat-associated kinase reveals a TFIIH complex that modulates HIV-1 transcription. EMBO J. 1997;16:2836-50 pubmed..These results define a cellular kinase complex whose activity is modulated by Tat to result in activation of HIV-1 trancription. ..
- Nogues G, Kadener S, Cramer P, Bentley D, Kornblihtt A. Transcriptional activators differ in their abilities to control alternative splicing. J Biol Chem. 2002;277:43110-4 pubmed..Rapid, highly processive transcription favors EDI exon skipping, whereas slower, less processive transcription favors inclusion. ..
- Wilusz J. Putting an 'End' to HIV mRNAs: capping and polyadenylation as potential therapeutic targets. AIDS Res Ther. 2013;10:31 pubmed publisher..This review describes these post-transcriptional novelties of HIV gene expression as well as their implications in viral biology and as possible targets for therapeutic intervention. ..
- Ivanov D, Kwak Y, Nee E, Guo J, García Martínez L, Gaynor R. Cyclin T1 domains involved in complex formation with Tat and TAR RNA are critical for tat-activation. J Mol Biol. 1999;288:41-56 pubmed..These results demonstrate that cyclin T1 interactions with Tat and TAR RNA are critical for activation of HIV-1 gene expression. ..
- Acker J, de Graaff M, Cheynel I, Khazak V, Kedinger C, Vigneron M. Interactions between the human RNA polymerase II subunits. J Biol Chem. 1997;272:16815-21 pubmed..These subunits, which are able to homodimerize and to interact, may constitute the nucleation center for polymerase assembly, by providing a large interface to most of the other subunits. ..
- Schlegel B, Green V, Ladias J, Parvin J. BRCA1 interaction with RNA polymerase II reveals a role for hRPB2 and hRPB10alpha in activated transcription. Proc Natl Acad Sci U S A. 2000;97:3148-53 pubmed..No other Pol II subunits tested inhibited activated transcription in these assays. Furthermore, hRPB10alpha, but not hRPB2, blocked Sp1-dependent activation. ..
- Chun R, Jeang K. Requirements for RNA polymerase II carboxyl-terminal domain for activated transcription of human retroviruses human T-cell lymphotropic virus I and HIV-1. J Biol Chem. 1996;271:27888-94 pubmed..Taken together, these observations address mechanistic corollaries between activators with(out) a linked CTD kinase and regulated transcription by RNA polymerase II moieties with(out) a CTD. ..
- Zhou C, Rana T. A bimolecular mechanism of HIV-1 Tat protein interaction with RNA polymerase II transcription elongation complexes. J Mol Biol. 2002;320:925-42 pubmed..These findings suggest that two Tat molecules are involved in performing various functions during a single round of HIV-1 mRNA synthesis. ..
- Jang K, Collins M, Latchman D. The human immunodeficiency virus tat protein increases the transcription of human Alu repeated sequences by increasing the activity of the cellular transcription factor TFIIIC. J Acquir Immune Defic Syndr. 1992;5:1142-7 pubmed..The significance of this effect for the life cycle of HIV and its interaction with infected cells is discussed. ..
- Nilson K, Price D. The Role of RNA Polymerase II Elongation Control in HIV-1 Gene Expression, Replication, and Latency. Genet Res Int. 2011;2011:726901 pubmed publisher..HIV, the causative agent of AIDS, is a worldwide health concern. It is hoped that knowledge of the mechanisms regulating the expression of the HIV genome will lead to treatments and ultimately a cure. ..
- Zhang H, Sun L, Liang J, Yu W, Zhang Y, Wang Y, et al. The catalytic subunit of the proteasome is engaged in the entire process of estrogen receptor-regulated transcription. EMBO J. 2006;25:4223-33 pubmed..These results revealed a mechanism by which the proteasome machinery is recruited in ER-mediated gene transcription. Our experiments also provided evidence implicating SRC coactivators in gene transcription elongation. ..
- Poon B, Chen I. Human immunodeficiency virus type 1 (HIV-1) Vpr enhances expression from unintegrated HIV-1 DNA. J Virol. 2003;77:3962-72 pubmed..These results attribute a new function to HIV-1 Vpr and implicate Vpr as a critical component in expression from unintegrated HIV-1 DNA...
- Kino T, Tsukamoto M, Chrousos G. Transcription factor TFIIH components enhance the GR coactivator activity but not the cell cycle-arresting activity of the human immunodeficiency virus type-1 protein Vpr. Biochem Biophys Res Commun. 2002;298:17-23 pubmed..These findings suggest that TFIIH participates in Vpr's GR coactivating activity, at a step beyond its interaction with p300/CBP. ..
- Kaehlcke K, Dorr A, Hetzer Egger C, Kiermer V, Henklein P, Schnoelzer M, et al. Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation. Mol Cell. 2003;12:167-76 pubmed..We propose that Tat acetylation may help in dissociating the Tat cofactor CyclinT1 from TAR RNA and serve to transfer Tat onto the elongating RNA polymerase II. ..
- Romano G, Kasten M, De Falco G, Micheli P, Khalili K, Giordano A. Regulatory functions of Cdk9 and of cyclin T1 in HIV tat transactivation pathway gene expression. J Cell Biochem. 1999;75:357-68 pubmed
- Agostini I, Navarro J, Bouhamdan M, Willetts K, Rey F, Spire B, et al. The HIV-1 Vpr co-activator induces a conformational change in TFIIB. FEBS Lett. 1999;450:235-9 pubmed..Our data show a correlation between the ability of Vpr-mutated proteins to stimulate transcription and their ability to induce a conformational change in TFIIB, indicating a functional relevance of the Vpr-TFIIB interaction. ..
- Mbonye U, Karn J. Control of HIV latency by epigenetic and non-epigenetic mechanisms. Curr HIV Res. 2011;9:554-67 pubmed
- Kershnar E, Wu S, Chiang C. Immunoaffinity purification and functional characterization of human transcription factor IIH and RNA polymerase II from clonal cell lines that conditionally express epitope-tagged subunits of the multiprotein complexes. J Biol Chem. 1998;273:34444-53 pubmed
- Yuan X, Zhao J, Zentgraf H, Hoffmann Rohrer U, Grummt I. Multiple interactions between RNA polymerase I, TIF-IA and TAF(I) subunits regulate preinitiation complex assembly at the ribosomal gene promoter. EMBO Rep. 2002;3:1082-7 pubmed..The results uncover an interphase for essential protein-protein interactions that facilitate Pol I preinitiation complex formation. ..
- Hu P, Wu S, Sun Y, Yuan C, Kobayashi R, Myers M, et al. Characterization of human RNA polymerase III identifies orthologues for Saccharomyces cerevisiae RNA polymerase III subunits. Mol Cell Biol. 2002;22:8044-55 pubmed..Our results provide a characterization of human RNA polymerase III and show that the RPC5 subunit is essential for transcription. ..
- Harrich D, McMillan N, Munoz L, Apolloni A, Meredith L. Will diverse Tat interactions lead to novel antiretroviral drug targets?. Curr Drug Targets. 2006;7:1595-606 pubmed..Nevertheless, Tat remains an attractive, virus-specific molecule and detailed understanding of specific protein interaction holds promise for future drug discovery. ..
- Suñé C, Garcia Blanco M. Transcriptional cofactor CA150 regulates RNA polymerase II elongation in a TATA-box-dependent manner. Mol Cell Biol. 1999;19:4719-28 pubmed..In addition, we also provide evidence suggesting a role for CA150 in the regulation of cellular transcriptional processes. ..
- Zhou M, Halanski M, Radonovich M, Kashanchi F, Peng J, Price D, et al. Tat modifies the activity of CDK9 to phosphorylate serine 5 of the RNA polymerase II carboxyl-terminal domain during human immunodeficiency virus type 1 transcription. Mol Cell Biol. 2000;20:5077-86 pubmed..These studies suggest that the ability of Tat to increase transcriptional elongation may be due to its ability to modify the substrate specificity of the CDK9 complex. ..
- Liu Y, Suñé C, Garcia Blanco M. Human immunodeficiency virus type 1 Tat-dependent activation of an arrested RNA polymerase II elongation complex. Virology. 1999;255:337-46 pubmed..These data indicate that Tat can activate elongation of RNA polymerase by modifying an already elongating transcription complex. The data also suggest the possibility that Tat can interact with initiation complexes. ..
- Suñé C, Hayashi T, Liu Y, Lane W, Young R, Garcia Blanco M. CA150, a nuclear protein associated with the RNA polymerase II holoenzyme, is involved in Tat-activated human immunodeficiency virus type 1 transcription. Mol Cell Biol. 1997;17:6029-39 pubmed..Furthermore, we found that functional Tat associates with the holoenzyme whereas activation-deficient Tat mutants do not. Thus, we propose that Tat action is transduced via an RNA polymerase II holoenzyme that contains CA150. ..
- Jeang K. Tat, Tat-associated kinase, and transcription. J Biomed Sci. 1998;5:24-7 pubmed..Here we review, in brief, the role of Tat-associated kinase in Tat-activated transcription. We discuss evidence that suggests involvement of TFIIH and/or P-TEFb. ..