PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-10 (10)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
more »
Year of Publication
1.  Role of Noncoding RNAs in the Regulation of P-TEFb Availability and Enzymatic Activity 
BioMed Research International  2014;2014:643805.
P-TEFb is a transcriptional factor that specifically regulates the elongation step of RNA polymerase II-dependent transcription and its activity strictly required for Human Immunodeficiency Virus (HIV) infection and during cardiac differentiation. P-TEFb role has emerged as a crucial regulator of transcription elongation and its activity found finely tuned in vivo at transcriptional level as well as posttranscriptionally by dynamic association with different multisubunit molecular particles. Both physiological and pathological cellular signals rapidly converge on P-TEFb regulation by modifying expression and activity of the complex to allow cells to properly respond to different stimuli. In this review we will give a panoramic view on P-TEFb regulation by noncoding RNAs in both physiological and pathological conditions.
doi:10.1155/2014/643805
PMCID: PMC3950470  PMID: 24701579
3.  Correction: Caffeine Prevents Transcription Inhibition and P-TEFb/7SK Dissociation Following UV-Induced DNA Damage 
PLoS ONE  2013;8(10):10.1371/annotation/753c6a63-2aea-4cb8-b38c-28db972d60df.
doi:10.1371/annotation/753c6a63-2aea-4cb8-b38c-28db972d60df
PMCID: PMC3792170
4.  SUMO-activating SAE1 transcription is positively regulated by Myc 
Myc protein plays a fundamental role in regulation of cell cycle, proliferation, differentiation and apoptosis by modulating the expression of a large number of targets. Here we report the transactivation ability of the human Myc protein to activate the SUMO-activating enzyme SAE1 transcription. We found that Myc activates SAE1 transcription via direct binding to canonical E-Boxes sequences located close to the SAE1 transcription start site. A recent report has highlighted the crucial role of the SAE gene expression in Myc mediated oncogenesis. Our study adds new insight in this context since we show here that Myc directly activates SAE1 transcription, suggesting that Myc oncogenic activity which depends on SAE1 is ensured by Myc itself through direct binding and transcriptional activation of SAE1 expression.
PMCID: PMC3365806  PMID: 22679563
Myc; SUMOylation; SAE1; transcription
5.  Myc and PI3K/AKT signaling cooperatively repress FOXO3a-dependent PUMA and GADD45a gene expression 
Nucleic Acids Research  2011;39(22):9498-9507.
Growth factor withdrawal inhibits cell cycle progression by stimulating expression of growth-arresting genes through the activation of Forkhead box O transcription factors such as FOXO3a, which binds to the FHRE-responsive elements of a number of target genes such as PUMA and GADD45a. Following exposure of cells to growth factors FOXO3a-mediated transcription is rapidly repressed. We determined that repression correlates with activation of PI3K/AKT pathway leading to FOXO3a phosphorylation and release of FOXO3a protein from PUMA and GADD45a chromatin. We show here that Myc significantly and selectively contributes to repression of FOXO-mediated expression of PUMA and GADD45a. We found that in Myc deprived cells inhibition of PUMA and GADD45a following serum stimulation is impaired and that Myc does not interfere with p53 induction of PUMA transcription. We observed that following activation, Myc is rapidly recruited to PUMA and GADD45a chromatin, with a concomitant switch in promoter occupancy from FOXO3a to Myc. Myc recruitment stimulates deacetylation of Histone H3 and H4 and methylation of lysine 9 in H3 (H3K9me2) on both PUMA and GADD45 chromatin. These data highlight a Myc role on cell growth by selectively inhibiting FOXO3a induced transcription of PUMA and GADD45.
doi:10.1093/nar/gkr638
PMCID: PMC3239183  PMID: 21835778
6.  Epigenetic reprogramming of Myc target genes 
Myc protein plays a fundamental role in regulation of cell cycle, proliferation, differentiation and apoptosis by modulating the expression of a large number of targets. Myc binding to its targets depends on the presence of the E-box binding sequence and by a chromatin context in which histone H3K4me3 lysine methylation favors Myc binding. Myc role in transcription is still an open question since Myc is able to either activate or repress target genes and the molecular mechanisms by which it exerts these functions span from chromatin remodeling to processive RNAPII elongation. Since the types and number of enzymes able to reversibly modify histones is recently growing, some of the acquisitions regarding Myc chromatin remodeling properties are being revaluated. Here, we summarize recent findings regarding the function of Myc in epigenetic reprogramming of its targets in transcription of differentiated as well as pluripotent cells.
PMCID: PMC3180057  PMID: 21969221
Myc; transcription; histones acetylation; histones methylation; epigenome
7.  Caffeine Prevents Transcription Inhibition and P-TEFb/7SK Dissociation Following UV-Induced DNA Damage 
PLoS ONE  2010;5(6):e11245.
Background
The mechanisms by which DNA damage triggers suppression of transcription of a large number of genes are poorly understood. DNA damage rapidly induces a release of the positive transcription elongation factor b (P-TEFb) from the large inactive multisubunit 7SK snRNP complex. P-TEFb is required for transcription of most class II genes through stimulation of RNA polymerase II elongation and cotranscriptional pre-mRNA processing.
Methodology/Principal Findings
We show here that caffeine prevents UV-induced dissociation of P-TEFb as well as transcription inhibition. The caffeine-effect does not involve PI3-kinase-related protein kinases, because inhibition of phosphatidylinositol 3-kinase family members (ATM, ATR and DNA-PK) neither prevents P-TEFb dissociation nor transcription inhibition. Finally, caffeine prevention of transcription inhibition is independent from DNA damage.
Conclusion/Significance
Pharmacological prevention of P-TEFb/7SK snRNP dissociation and transcription inhibition following UV-induced DNA damage is correlated.
doi:10.1371/journal.pone.0011245
PMCID: PMC2888590  PMID: 20574533
8.  Inhibition of Tat activity by the HEXIM1 protein 
Retrovirology  2005;2:42.
Background
The positive transcription elongation factor b (P-TEFb) composed by CDK9/CyclinT1 subunits is a dedicated co-factor of HIV transcriptional transactivator Tat protein. Transcription driven by the long terminal repeat (LTR) of HIV involves formation of a quaternary complex between P-TEFb, Tat and the TAR element. This recruitment is necessary to enhance the processivity of RNA Pol II from the HIV-1 5' LTR promoter. The activity of P-TEFb is regulated in vivo and in vitro by the HEXIM1/7SK snRNA ribonucleic-protein complex.
Results
Here we report that Tat transactivation is effectively inhibited by co-expression of HEXIM1 or its paralog HEXIM2. HEXIM1 expression specifically represses transcription mediated by the direct activation of P-TEFb through artificial recruitment of GAL4-CycT1. Using appropriate HEXIM1 mutants we determined that effective Tat-inhibition entails the 7SK snRNA basic recognition motif as well as the C-terminus region required for interaction with cyclin T1. Enhanced expression of HEXIM1 protein modestly affects P-TEFb activity, suggesting that HEXIM1-mediated repression of Tat activity is not due to a global inhibition of cellular transcription.
Conclusion
These results point to a pivotal role of P-TEFb for Tat's optimal transcription activity and suggest that cellular proteins that regulate P-TEFb activity might exert profound effects on Tat function in vivo.
doi:10.1186/1742-4690-2-42
PMCID: PMC1183248  PMID: 15992410
9.  The FCP1 phosphatase interacts with RNA polymerase II and with MEP50 a component of the methylosome complex involved in the assembly of snRNP 
Nucleic Acids Research  2003;31(3):999-1005.
RNA polymerase II transcription is associated with cyclic phosphorylation of the C-terminal domain (CTD) of the large subunit of RNA polymerase II. To date, FCP1 is the only specific CTD phosphatase, which is required for general transcription and cell viability. To identify FCP1-associated proteins, we constructed a human cell line expressing epitope-tagged FCP1. In addition to RAP74, a previously identified FCP1 interacting factor, we determined that FCP1-affinity purified extracts contain RNAPII that has either a hyper- or a hypo-phosphorylated CTD. In addition, by mass spectrometry of affinity purified FCP1-associated factors, we identified a novel FCP1-interacting protein, named MEP50, a recently described component of the methylosome complex that binds to the snRNP’s Sm proteins. We found that FCP1 specifically interacts with components of the spliceosomal U small nuclear ribonucleoproteins. These results suggest a putative role of FCP1 CTD-phosphatase in linking the transcription elongation with the splicing process.
PMCID: PMC149217  PMID: 12560496
10.  Transcription activation by targeted recruitment of the RNA polymerase II CTD phosphatase FCP1 
Nucleic Acids Research  2001;29(17):3539-3545.
Human FCP1 in association with RNAP II reconstitutes a highly specific CTD phosphatase activity and is required for recycling RNA polymerase II (RNAP II) in vitro. Here we demonstrate that targeted recruitment of FCP1 to promoter templates, through fusion to a DNA-binding domain, stimulates transcription. We demonstrate that a short region at the C-terminus of the FCP1 protein is required and sufficient for activation, indicating that neither the N-terminal phosphatase domain nor the BRCT domains are required for transcription activity of DNA-bound FCP1. In addition, we demonstrate that the C-terminus region of FCP1 suffices for efficient binding in vivo to the RAP74 subunit of TFIIF and is also required for the exclusive nuclear localization of the protein. These findings suggest a role for FCP1 as a positive regulator of RNAP II transcription.
PMCID: PMC55871  PMID: 11522823

Results 1-10 (10)