A5026093084- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Protein Degradation and Inhibitors
- Estrogen and related hormone effects
- Cytokine Signaling Pathways and Interactions
- RNA modifications and cancer
- Virus-based gene therapy research
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Retinoids in leukemia and cellular processes
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- Herpesvirus Infections and Treatments
- Nuclear Receptors and Signaling
- Immunotherapy and Immune Responses
- Mosquito-borne diseases and control
- Epigenetics and DNA Methylation
- HIV/AIDS Research and Interventions
- Histone Deacetylase Inhibitors Research
University of California, San Francisco
2015-2024
Case Western Reserve University
2003-2014
University School
2003-2010
University of Michigan
2009
Hokkaido University
1994-2002
Howard Hughes Medical Institute
1997-2002
Nagoya University
1994
Flavopiridol (L86-8275, HMR1275) is a cyclin-dependent kinase (Cdk) inhibitor that in clinical trials as cancer treatment because of its antiproliferative properties. We found the flavonoid potently inhibited transcription by RNA polymerase II <i>in vitro</i> blocking transition into productive elongation, step controlled P-TEFb. The ability P-TEFb to phosphorylate carboxyl-terminal domain large subunit was flavopiridol with a<i>K</i> <sub>i</sub> 3 nm. Interestingly, drug not competitive...
The persistence of latently infected cells in patients under combinatory antiretroviral therapy (cART) is a major hurdle to HIV-1 eradication. Strategies purge these reservoirs are needed and activation viral gene expression one promising strategy. Bromodomain Extraterminal (BET) bromodomain inhibitors (BETi) compounds able reactivate latent proviruses positive transcription elongation factor b (P-TEFb)-dependent manner. In this study, we tested the reactivation potential protein kinase C...
The elongation of transcription is a highly regulated process that requires negative and positive effectors. By binding the double-stranded stem in transactivation response (TAR) element, RD protein from factor (NELF) inhibits basal long terminal repeat human immunodeficiency virus type 1 (HIVLTR). Tat its cellular cofactor, b (P-TEFb), overcome this effect. Cdk9 P-TEFb also phosphorylates at sites next to RNA recognition motif. A mutant mimics phosphorylated form no longer binds TAR nor...
The human immunodeficiency virus encodes the transcriptional transactivator Tat, which binds to transactivation response (TAR) RNA stem–loop in viral long terminal repeat (LTR) and increases rates of elongation rather than initiation transcription by polymerase II (Pol II). In this study, we demonstrate that Tat directly cyclin-dependent kinase 7 (CDK7), leads productive interactions between CDK-activating (CAK) complex TFIIH. activates phosphorylation carboxy-terminal domain (CTD) Pol CAK...
By phosphorylating elongation factors and the C-terminal domain of RNA polymerase II, positive transcription factor b (P-TEFb) is critical kinase for co-transcriptional processing eukaryotic genes. It exists in inactive small nuclear ribonucleoprotein (7SK snRNP) active (free P-TEFb) complexes cells. The P-TEFb equilibrium determines state cellular activation, proliferation, differentiation. Free P-TEFb, which required growth, can be recruited to II via factors, BRD4, or super complex (SEC)....
The role of the negative elongation factor (NELF) in maintaining HIV latency was investigated following small hairpin RNA (shRNA) knockdown NELF-E subunit, a condition that induced high levels proviral transcription latently infected Jurkat T cells. Chromatin immunoprecipitation (ChIP) assays showed latent proviruses accumulate polymerase II (RNAP II) on 5' long terminal repeat (LTR) but not 3' LTR. NELF colocalizes with RNAP II, and its level increases induction. pause sites provirus were...
DNA damage response (DDR) involves dramatic transcriptional alterations, the mechanisms of which remain ill defined. Here, we show that following genotoxic stress, RNA-binding motif protein 7 (RBM7) stimulates RNA polymerase II (Pol II) transcription and promotes cell viability by activating positive elongation factor b (P-TEFb) via its release from inhibitory 7SK small nuclear ribonucleoprotein (7SK snRNP). This is mediated activation p38MAPK, triggers enhanced binding RBM7 with core...
The Tat proteins of HIV-1 and simian immunodeficiency virus (SIV) are essential for activating viral transcription. In addition, stimulates nuclear factor κB (NF-κB) signaling pathways to regulate gene expression although its molecular mechanism is unclear. Here, we report that directly activates NF-κB through the interaction with TRAF6, which an upstream molecule canonical pathway. This increases TRAF6 oligomerization auto-ubiquitination, as well synthesis K63-linked polyubiquitin chains...
ABSTRACT By binding to the transactivation response element (TAR) RNA, transcriptional transactivator (Tat) from human immunodeficiency virus increases rates of elongation rather than initiation viral transcription. Two cyclin-dependent serine/threonine kinases, CDK7 and CDK9, which phosphorylate C-terminal domain RNA polymerase II, have been implicated in Tat vivo vitro. In this report, we demonstrate that is kinase component positive transcription factor b (P-TEFb) complex, can activate...
Autophagy is a homeostatic mechanism of lysosomal degradation. Defective autophagy has been linked to various disorders such as impaired control pathogens and neurodegeneration. regulated by complex array signaling pathways that act upstream proteins. Little known about the role altered regulatory in associated with defective autophagy. In particular, it not if inhibit modulation pathways. Cells infected HIV-1 blocked rapamycin-induced CD40-induced autophagic killing Toxoplasma gondii...
Recent efforts have been paid to identify previously unrecognized HIV-1 latency-promoting genes (LPGs) that can potentially be targeted for eradication of latent reservoirs. From our earlier orthologous RNAi screens host factors regulating replication, we identified the nucleolar protein NOP2/NSUN1, a m5C RNA methyltransferase (MTase), is an restriction factor. Loss- and gain-of-function analyses confirmed NOP2 restricts replication. Depletion promotes reactivation latently infected...
The transcriptional transactivator Tat from HIV binds to the transactivation response element (TAR) RNA increase rates of elongation viral transcription. Human cyclin T supports these interactions between and TAR. In this study, we report sequence mouse identify residues positions 1 281 in human that bind Mouse weakly is unable facilitate Reciprocal exchanges cysteine tyrosine at position 261 proteins also render inactive active. These findings reveal molecular basis for restriction rodent cells.
Transcriptional elongation by RNA polymerase II (RNAPII) is regulated the positive transcription factor b (P-TEFb).P-TEFb composed of Cdk9 and C-type cyclin T1 (CycT1), CycT2a, CycT2b, or CycK.The role C-terminal region CycT1 CycT2 remains unknown.In this report, we demonstrate that these sequences are essential for activation P-TEFb via DNA, i.e., when tethered upstream downstream promoters coding sequences.A histidine-rich stretch, which conserved between in region, bound domain...
Transcriptional cyclin-dependent kinases (CDKs) regulate RNA polymerase II initiation and elongation as well cotranscriptional mRNA processing. In this report, we describe an important role for CDK12 in the epidermal growth factor (EGF)-induced c-FOS proto-oncogene expression mammalian cells. This kinase was found exon junction complexes (EJC) together with SR proteins thus recruited to II. cells depleted of or eukaryotic translation 4A3 (eIF4A3) from EJC, EGF induced fewer transcripts....
ABSTRACT Human endogenous retroviruses (HERVs) make up 8% of the human genome. The HERV type K (HERV-K) HML-2 (HK2) family contains proviruses that are most recent entrants into germ line and transcriptionally active. In HIV-1 infection cancer, HK2 genes produce retroviral particles appear to be infectious, yet replication capacity these viruses potential pathogenicity has been difficult ascertain. this report, we screened efficacy commercially available reverse transcriptase inhibitors...