Research Topics
Genomes and Genes | Adriana LopesSummaryAffiliation: University of California Country: USA Publications
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Publications
Unmodified histone H3K4 and DNA-dependent protein kinase recruit autoimmune regulator to target genesKristina Zumer
Department of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland
Mol Cell Biol 32:1354-62. 2012..Importantly, mutations in the putative DNA-binding residues in its SAND domain had no effect on the transcriptional effects of AIRE. Thus, AIRE is recruited to TRA genes in chromatin via cooperative interactions with H3K4me0 and DNA-PK...- Interactions between Nef and AIP1 proliferate multivesicular bodies and facilitate egress of HIV-1Luciana J Costa
Molecular Virology Laboratory, Dep of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Retrovirology 3:33. 2006..In this report, we investigated further the ability of Nef to facilitate the replication of HIV-1... - 7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcriptionB Matija Peterlin
Department of Medicine, Rosalind Russel Medical Research Center, University of California, San Francisco, CA, USA
Wiley Interdiscip Rev RNA 3:92-103. 2012..Regulated release of P-TEFb determines the expression pattern of many of the genes that respond to environmental stimuli and regulate growth, proliferation, and differentiation of cells... 
Controlling the elongation phase of transcription with P-TEFbB Matija Peterlin
Department of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, San Francisco, California 94143, USA
Mol Cell 23:297-305. 2006..Phylogenetic analyses of the components of the human elongation control machinery indicate that the number of mechanisms utilized to regulate P-TEFb function increased as organisms developed more complex developmental patterns...- Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response elementKoh Fujinaga
Department of Medicine, Rosalind Russell Medical Research Center, University of California at San Francisco, 3rd and Parnassus Avenue, San Francisco, CA 94143 0703, USA
Mol Cell Biol 24:787-95. 2004..These results better define the transition from abortive to productive transcription and thus replication of HIV... - Interaction between P-TEFb and the C-terminal domain of RNA polymerase II activates transcriptional elongation from sites upstream or downstream of target genesRan Taube
Howard Hughes Medical Institute, Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0703, USA
Mol Cell Biol 22:321-31. 2002..This binding was required for the subsequent expression of full-length transcripts from target genes. Thus, P-TEFb could mediate effects of enhancers on the elongation of transcription... - Optimized chimeras between kinase-inactive mutant Cdk9 and truncated cyclin T1 proteins efficiently inhibit Tat transactivation and human immunodeficiency virus gene expressionKoh Fujinaga
Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0703, USA
J Virol 76:10873-81. 2002..This chimera inhibited Tat transactivation and HIV gene expression in human cells. Therefore, this dominant-negative kinase-inactive mutant Cdk9.hCycT1 chimera could be used for antiviral gene therapy... - Suberoylanilide hydroxamic acid reactivates HIV from latently infected cellsXavier Contreras
Department of Medicine, University of California, San Francisco, California 94143, USA
J Biol Chem 284:6782-9. 2009..Thus SAHA, which is a Food and Drug Administration-approved drug, might be considered to accelerate the decay of the latent reservoir in HAART-treated infected humans... 
Transcriptional interference antagonizes proviral gene expression to promote HIV latencyTina Lenasi
Department of Medicine, Rosalind Russell Medical Research Center, University of California San Francisco, San Francisco, CA 94143, USA
Cell Host Microbe 4:123-33. 2008..Collectively, our findings suggest that TI contributes significantly to HIV latency and should be considered when attempting to purge the latent reservoir...- AIRE recruits P-TEFb for transcriptional elongation of target genes in medullary thymic epithelial cellsIrena Oven
Department of Medicine, Rosalind Russell Medical Research Center, University of California San Francisco, San Francisco, California 94143 0703, USA
Mol Cell Biol 27:8815-23. 2007..Our findings reveal critical steps by which AIRE regulates the transcription of genes that control central tolerance in the thymus... - Transcriptional activity and substrate recognition of cyclin T2 from P-TEFbTakeshi Kurosu
Department of Medicine, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA 94143 0703, USA
Gene 343:173-9. 2004..Moreover, this domain bound RNAPII via its CTD and PIE-1 blocked its effects. Thus, CycT2 not only contains two domains that target RNAPII but this substrate recognition is necessary for its transcriptional activity via DNA... - A new paradigm in eukaryotic biology: HIV Tat and the control of transcriptional elongationMatjaz Barboric
Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, USA
PLoS Biol 3:e76. 2005 - Newly identified host factors modulate HIV replicationYong-Hui Zheng
Department of Medicine, Rosalind Russell Arthritis Research Center, University of California, San Francisco, San Francisco, CA 94143, USA
Immunol Lett 97:225-34. 2005 - Intracellular immunity to HIV-1: newly defined retroviral battles inside infected cellsYong Hui Zheng
Department of Medicine, Rosalind Russell Arthritis Research Center, University of California, San Francisco, CA 94143 0703, USA
Retrovirology 2:25. 2005..These processes also offer a tantalizing glimpse at basic cellular mechanisms that might restrict the movement of mobile genetic elements and protect the genome... - Charting HIV's remarkable voyage through the cell: Basic science as a passport to future therapyWarner C Greene
Gladstone Institute of Virology and Immunology, Department of Medicine, University of California at San Francisco, San Francisco, California, USA
Nat Med 8:673-80. 2002..Understanding the dynamic interplay of host cell and virus is essential to the effort to eradicate HIV... - Distal regulation of alternative splicing by splicing enhancer in equine beta-casein intron 1Tina Lenasi
University of Ljubljana, Biotechnical Faculty, Department of Animal Science, Groblje, Slovenia
RNA 12:498-507. 2006..Thus, the ISE1 remains in close proximity to the mRNA exit groove throughout transcription and influences all weak exons as soon as they are copied... - P-TEFb containing cyclin K and Cdk9 can activate transcription via RNAXin Lin
Department of Medicine, University of California at San Francisco, California 94143 0703, USA
J Biol Chem 277:16873-8. 2002..Moreover, these transcriptional effects required the CTD of RNAPII in cells. Thus, CycK functions as P-TEFb only via RNA, which suggests the presence of cellular RNA-bound activators that require CycK for their transcriptional activity... - Runx1 binds positive transcription elongation factor b and represses transcriptional elongation by RNA polymerase II: possible mechanism of CD4 silencingHuimin Jiang
Department of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, 94143 0703, USA
Mol Cell Biol 25:10675-83. 2005..These results suggest that active repression by Runx1 occurs by blocking the elongation by RNAPII, which may contribute to CD4 silencing during T-cell development... - Hide, shield and strike back: how HIV-infected cells avoid immune eradicationB Matija Peterlin
Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, California 94143 0703, USA
Nat Rev Immunol 3:97-107. 2003..A better understanding of these strategies might lead to new approaches in the fight against AIDS... - A model of repression: CTD analogs and PIE-1 inhibit transcriptional elongation by P-TEFbFan Zhang
Departments of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA 94143, USA
Genes Dev 17:748-58. 2003..It binds CycT1 via an alanine-containing heptapeptide repeat and inhibits transcriptional elongation. Thus, our findings reveal a new mechanism by which repressors inhibit eukaryotic transcription... - Transcriptional profiles of latent human immunodeficiency virus in infected individuals: effects of Tat on the host and reservoirXin Lin
Department of Medicine, San Francisco General Hospital, Center For AIDS Research and Department of Pathology, University of California, San Francisco, USA
J Virol 77:8227-36. 2003..In their cells, T-cell activation or exogenous Tat could induce viral replication equivalently. Thus, P-TEFb could activate the majority of the latent HIV, in this case by Tat... - Human APOBEC3F is another host factor that blocks human immunodeficiency virus type 1 replicationYong Hui Zheng
Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, 3rd and Parnassus Ave, San Francisco, CA 94143 0703, USA
J Virol 78:6073-6. 2004..Thus, APOBEC family members might have evolved as a general defense mechanism of the body against retroviruses, retrotransposons, and other mobile genetic elements... - 7SK snRNP/P-TEFb couples transcription elongation with alternative splicing and is essential for vertebrate developmentMatjaz Barboric
Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143 0703, USA
Proc Natl Acad Sci U S A 106:7798-803. 2009..These findings reveal a key role for P-TEFb in coupling transcription elongation with alternative splicing, and suggest that maintaining core 7SK snRNP is essential for vertebrate development... - Human p32 protein relieves a post-transcriptional block to HIV replication in murine cellsYong Hui Zheng
Department of Medicine, Rosalind Russell Medical Research Center, Mt Zion Research Building Room N231, 2340 Sutter Street, University of California, San Francisco, CA 94115, USA
Nat Cell Biol 5:611-8. 2003..A single substitution in hp32 of Gly 35 to Asp 35, which is found in mp32, abrogates this activity. Thus, hp32 overcomes an important post-transcriptional block to HIV replication in murine cells... - Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFbMatjaz Barboric
Department of Medicine, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA 94143 0703, USA
EMBO J 24:4291-303. 2005..We propose a model where the interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct its binding to P-TEFb and subcellular localization that culminates in the inhibition of transcription... - APOBEC3 proteins and reverse transcriptionRenato S Aguiar
Department of Medicine, Microbiology and Immunology, University of California, San Francisco UCSF, 533 Parnassus Avenue U422, San Francisco, CA 94143 0703, USA
Virus Res 134:74-85. 2008..Together, these proteins provide strong and immediate intracellular immunity against incoming pathogens and restrict the movement of mobile genetic elements protecting the genome... - Ubiquitylation of Cdk9 by Skp2 facilitates optimal Tat transactivationMatjaz Barboric
Rosalind Russell Medical Research Center, Department of Medicine, University of California, San Francisco, 94143, USA
J Virol 79:11135-41. 2005..Thus, our findings underscore the requirement of ubiquitylation for the coactivator function in regulating HIV-1 transcriptional elongation... - c-Myc recruits P-TEFb for transcription, cellular proliferation and apoptosisSatoshi Kanazawa
Departments of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143 0703, USA
Oncogene 22:5707-11. 2003..Inhibiting P-TEFb blocks the transcription of its target genes as well as cellular proliferation and apoptosis induced by c-Myc... - Major histocompatibility complex class II transcriptional platform: assembly of nuclear factor Y and regulatory factor X (RFX) on DNA requires RFX5 dimersNabila Jabrane-Ferrat
Department of Surgery, University of California-San Francisco, San Francisco, CA 94115-0703, USA
Mol Cell Biol 22:5616-25. 2002..These findings offer one explanation of why in the Bare Lymphocyte Syndrome, which is a congenital severe combined immunodeficiency, MHC-II promoters are bare when any subunit of RFX is mutated or missing... - Tat-SIRT1 tangoDalibor Blazek
Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, San Francisco, CA 94143 0703, USA
Mol Cell 29:539-40. 2008..2008) report that the human immunodeficiency virus (HIV) transactivator Tat inhibits the SIRT1 deacetylase, resulting in increased acetylation of the NF-kappaB p65 subunit and subsequently in T cell hyperactivation... - Vpr.A3A chimera inhibits HIV replicationRenato S Aguiar
Department of Medicine, Microbiology, and Immunology, University of California at San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143 0703, USA
J Biol Chem 283:2518-25. 2008..Thus, by targeting appropriately a potent single domain cytidine deaminase, we rendered HIV and simian immunodeficiency virus restriction resistant to Vif... - Structure-based computational database screening, in vitro assay, and NMR assessment of compounds that target TAR RNAKenneth E Lind
Department of Pharmaceutical Chemistry, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
Chem Biol 9:185-93. 2002..Eleven compounds (between 0.1 and 1 microM) inhibited the Tat-TAR interaction, and some inhibited Tat transactivation in cells. NMR spectra verified specific binding to the 5' bulge and no interaction with other regions of TAR... - A minimal chimera of human cyclin T1 and tat binds TAR and activates human immunodeficiency virus transcription in murine cellsKoh Fujinaga
Departments of Medicine, Microbiology and Immunology, UCSF-Mt. Zion Cancer Center, University of California at San Francisco, 2340 Sutter Street, San Francisco, CA 94143-0703, USA
J Virol 76:12934-9. 2002..We conclude that this minimal chimera not only reproduces the high-affinity binding among P-TEFb, Tat, and TAR but also will be invaluable for determining the three-dimensional structure of this RNA-protein complex... - VP16 and ubiquitin; binding of P-TEFb via its activation domain and ubiquitin facilitates elongation of transcription of target genesTakeshi Kurosu
Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, San Francisco, CA 94115, USA
Curr Biol 14:1112-6. 2004..Thus, the ubiquitylation of AADs increases their interaction with P-TEFb and augments rates of elongation of transcription... - Enhanced replication and pathogenesis of Moloney murine leukemia virus in mice defective in the murine APOBEC3 geneAudrey Low
Department of Molecular Biology and Biochemistry, and Cancer Research Institute, University of California, Irvine, California 92697 3905, USA
Virology 385:455-63. 2009..These studies indicate that mA3 restricts replication and pathogenesis of M-MuLV in vivo... - Genetic analysis of P-TEFb function via heterologous nucleic acid tethering systemsQintong Li
Departments of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California San Francisco, San Francisco, CA 94143, USA
Methods 48:375-80. 2009..In this paper, we describe various heterologous nucleic acid tethering systems that can be used to examine transcription factors that function via P-TEFb... - Mutation in a winged-helix DNA-binding motif causes atypical bare lymphocyte syndromeNada Nekrep
Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143 0703, USA
Nat Immunol 3:1075-81. 2002..Its wild-type counterpart restored binding of the RFX complex to DNA, transcription of all MHC class II genes and the appearance of these determinants on the surface of BLS cells... - Nef increases the synthesis of and transports cholesterol to lipid rafts and HIV-1 progeny virionsYong Hui Zheng
Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143 0703, USA
Proc Natl Acad Sci U S A 100:8460-5. 2003..Thus, Nef also transports newly synthesized cholesterol to the site of viral budding. As such, it provides essential building blocks for the formation of viruses that replicate optimally in the host... - Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in AireMaureen A Su
Diabetes Center, Department of Pediatric, UCSF, San Francisco, California 94143, USA
J Clin Invest 118:1712-26. 2008..Together, these results may demonstrate a mechanism by which autoimmune predisposition to phenotypes distinct from APS 1 can be mediated in a dominant-negative fashion by Aire... - Nef binds p6* in GagPol during replication of human immunodeficiency virus type 1Luciana J Costa
Department of Medicine, University of California San Francisco, UCSF Mt Zion Cancer Center, 2340 Sutter Street, San Francisco, CA 94115, USA
J Virol 78:5311-23. 2004..Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1... - Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFbDalibor Blazek
Department of Medicine, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, CA 94143-0703, USA
Nucleic Acids Res 33:7000-10. 2005..Our results suggest that two independent regions in HEXIM1 form oligomers to incorporate P-TEFb into the large complex and determine the inhibition of transcriptional elongation... - Differential chromatin looping regulates CD4 expression in immature thymocytesHuimin Jiang
Departments of Medicine, Microbiology, and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, San Francisco, California 94143, USA
Mol Cell Biol 28:907-12. 2008..Thus, differential looping and decoying of P-TEFb away from the promoter mediate active repression of the CD4 gene during thymocyte development... - HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activates HIV transcriptionXavier Contreras
Department of Medicine, Rosalind Russell Medical Research Center, University of California San Francisco, San Francisco, California, USA
PLoS Pathog 3:1459-69. 2007..Thus, our studies reveal how HIV transcription is induced by HMBA and suggest how modifications in the equilibrium between active and inactive P-TEFb could contribute to cell differentiation... - P bodies inhibit retrotransposition of endogenous intracisternal a particlesChunye Lu
Department of Medicine, Microbiology, University of California at San Francisco, San Francisco, California 94143 0703, USA
J Virol 85:6244-51. 2011..Although IAP mRNA localized to P bodies, Gag was targeted to the endoplasmic reticulum (ER), from which IAP buds. Thus, by sequestering IAP mRNA away from Gag, P bodies inhibit rather than promote IAP retrotransposition... - Hexim1 sequesters positive transcription elongation factor b from the class II transactivator on MHC class II promotersJiri Kohoutek
Department of Medicine, Rosalind Russell Medical Research Center, University of California, San Francisco, CA 94143-0703, USA
Proc Natl Acad Sci U S A 103:17349-54. 2006..Thus, modulating ratios between active and inactive P-TEFb complexes is an additional mechanism of regulating transcriptional activators such as CIITA... - Subunit H of the V-ATPase binds to the medium chain of adaptor protein complex 2 and connects Nef to the endocytic machineryMatthias Geyer
Department of Medicine, University of California, San Francisco, California 94143 0703, USA
J Biol Chem 277:28521-9. 2002..Finally, blocking the expression of V1H decreased the enhancement of virion infectivity by Nef. Thus, V1H can function as an adaptor for interactions between Nef and AP-2... - HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cellsMetka Lenassi
Departments of Medicine, Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA
Traffic 11:110-22. 2010..Thus, HIV-infected cells export Nef in bioactive vesicles, which facilitate the depletion of CD4(+) T cells that is a hallmark of acquired immunodeficiency syndrome (AIDS)... - Sequential modifications in class II transactivator isoform 1 induced by lipopolysaccharide stimulate major histocompatibility complex class II transcription in macrophagesGorazd Drozina
Department of Medicine, Rosalind Russell Medical Research Center, University of California San Francisco, San Francisco, California 94143, USA
J Biol Chem 281:39963-70. 2006..Subsequent polyubiquitylation results in the degradation of CIITA isoform 1. Thus, the signaling cascade from Toll-like receptor 4 to CIITA isoform 1 represents one connection between innate and adaptive immunity in macrophages...
Research Grants
- CIITA and MHC II TranscriptionBORIS PETERLIN; Fiscal Year: 2006..Collectively, these studies will reveal the normal physiology of CIITA, why it oligomerizes and shuttles, and create new tools to manipulate the immune response in health and disease. ..
- Tat TransactivationB Matija Peterlin; Fiscal Year: 2007..These studies will reveal the complex RNA-protein world of P-TEFb and how HIV subverts these cellular complexes for its replication in cells. ..
- CIITA and MHC II TranscriptionBORIS PETERLIN; Fiscal Year: 2007..Collectively, these studies will reveal the normal physiology of CIITA, why it oligomerizes and shuttles, and create new tools to manipulate the immune response in health and disease. ..
- Tat TransactivationBORIS MATIJA PETERLIN; Fiscal Year: 2011..This proposal will investigate how Tat uses these complexes for optimal HIV replication and how these Cdks could be manipulated pharmacologically in the future. ..
- Mechanism of HIV 1 Nef ActionBORIS PETERLIN; Fiscal Year: 2006..Moreover, properties of an unusual allele of Nef, from HIV-1/F12 will be investigated for its dominant negative properties in viral replication. ..
- CIITA and MHC II TranscriptionBORIS PETERLIN; Fiscal Year: 2003..Collectively, these studies will reveal the normal physiology of CIITA, why it oligomerizes and shuttles, and create new tools to manipulate the immune response in health and disease. ..
- Tat TransactivationBORIS PETERLIN; Fiscal Year: 2004..Findings in vitro will be correlated with chromatin immunoprecipitations in cells. ..
- Tat TransactivationBORIS MATIJA PETERLIN; Fiscal Year: 2010..These studies will reveal the complex RNA-protein world of P-TEFb and how HIV subverts these cellular complexes for its replication in cells. ..