Search tips
Search criteria

Results 1-9 (9)

Clipboard (0)

Select a Filter Below

Year of Publication
2.  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.
PMCID: PMC3792170
3.  Identification of Novel AR-Targeted MicroRNAs Mediating Androgen Signalling through Critical Pathways to Regulate Cell Viability in Prostate Cancer 
PLoS ONE  2013;8(2):e56592.
MicroRNAs (miRNAs) have been recognized as significantly involved in prostate cancer (PCa). Since androgen receptor (AR) plays a central role in PCa carcinogenesis and progression, it is imperative to systematically elucidate the causal association between AR and miRNAs, focusing on the molecular mechanisms by which miRNAs mediate AR signalling. In this study, we performed a series of time-course microarrays to observe the dynamic genome-wide expressions of mRNAs and miRNAs in parallel in hormone-sensitive prostate cancer LNCaP cells stimulated by androgen. Accordingly, we introduced Response Score to identify AR target miRNAs, as well as Modulation Score to identify miRNA target mRNAs. Based on theoretical identification and experimental validation, novel mechanisms addressing cell viability in PCa were unravelled for 3 miRNAs newly recognized as AR targets. (1) miR-19a is directly up-regulated by AR, and represses SUZ12, RAB13, SC4MOL, PSAP and ABCA1, respectively. (2) miR-27a is directly up-regulated by AR, and represses ABCA1 and PDS5B. (3) miR-133b is directly up-regulated by AR, and represses CDC2L5, PTPRK, RB1CC1, and CPNE3, respectively. Moreover, we found miR-133b is essential to PCa cell survival. Our study gives certain clues on miRNAs mediated AR signalling to cell viability by influencing critical pathways, especially by breaking through androgen’s growth restriction effect on normal prostate tissue.
PMCID: PMC3579835  PMID: 23451058
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.  Reactive Oxygen Species Regulate the Levels of Dual Oxidase (Duox1-2) in Human Neuroblastoma Cells 
PLoS ONE  2012;7(4):e34405.
Dual Oxidases (DUOX) 1 and 2 are efficiently expressed in thyroid, gut, lung and immune system. The function and the regulation of these enzymes in mammals are still largely unknown. We report here that DUOX 1 and 2 are expressed in human neuroblastoma SK-N-BE cells as well as in a human oligodendrocyte cell line (MO3-13) and in rat brain and they are induced by platelet derived growth factor (PDGF). The levels of DUOX 1 and 2 proteins and mRNAs are induced by reactive oxygen species (ROS) produced by the membrane NADPH oxidase. As to the mechanism, we find that PDGF stimulates membrane NADPH oxidase to produce ROS, which stabilize DUOX1 and 2 mRNAs and increases the levels of the proteins. Silencing of gp91phox (NOX2), or of the other membrane subunit of NADPH oxidase, p22phox, blocks PDGF induction of DUOX1 and 2. These data unravel a novel mechanism of regulation of DUOX enzymes by ROS and identify a circuitry linking NADPH oxidase activity to DUOX1 and 2 levels in neuroblastoma cells.
PMCID: PMC3327694  PMID: 22523549
6.  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.
PMCID: PMC3239183  PMID: 21835778
7.  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
8.  Caffeine Prevents Transcription Inhibition and P-TEFb/7SK Dissociation Following UV-Induced DNA Damage 
PLoS ONE  2010;5(6):e11245.
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.
Pharmacological prevention of P-TEFb/7SK snRNP dissociation and transcription inhibition following UV-induced DNA damage is correlated.
PMCID: PMC2888590  PMID: 20574533
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

Results 1-9 (9)