How Much Did the Rise of Energy Prices Contribute to the EUR/USD Exchange Rate Reaching Parity in 2022?

In July 2022, the EUR/USD exchange rate hit parity for the first time in 20 years, meaning that 1 USD = 1 Euro. Prior to this, the Euro was stronger relative to the USD. During this time, Oil and Gas prices were also rising due to the Russia-Ukraine war as Russia is a main exporter of energy to the Euro Area. In my research, I want to analyze how much this increase in the energy prices, due to the geopolitical environment, pushed the EUR/USD to reach parity in 2022. I used monthly data from January 1999 to February 2023 for the EUR/USD exchange rate, Brent oil price, Henry Hub gas price, US interest rate, and Euro Area interest rate. For the analysis, I conducted a vector autoregression to conclude that an increase in the energy prices over an 8-month period led to the exchange rate to change by -0.0115 and the energy prices explain 26.42% of the decrease in the EUR/USD exchange rate. Therefore, as the Euro Area was reliant on Russian energy, it relatively depreciated and as the US is a net exporter of energy it relatively appreciated, helping bring the exchange rate to parity. Thus, the increase in energy prices did contribute to the EUR/USD exchange rate to reach parity to a certain extent, but there are other factors that impacted this exchange rate

Phosphorylation of Daxx by ATM contributes to DNA damage-induced p53 activation.

p53 plays a central role in tumor suppression. It does so by inducing anti-proliferative processes as a response to various tumor-promoting stresses. p53 is regulated by the ubiquitin ligase Mdm2. The optimal function of Mdm2 requires Daxx, which stabilizes Mdm2 through the deubiquitinase Hausp/USP7 and also directly promotes Mdm2's ubiquitin ligase activity towards p53. The Daxx-Mdm2 interaction is disrupted upon DNA damage. However, both the mechanisms and the consequence of the Daxx-Mdm2 dissociation are not understood. Here we show that upon DNA damage Daxx is phosphorylated in a manner that is dependent on ATM, a member of the PI 3-kinase family that orchestrates the DNA damage response. The main phosphorylation site of Daxx is identified to be Ser564, which is a direct target of ATM. Phosphorylation of endogenous Daxx at Ser564 occurs rapidly during the DNA damage response and precedes p53 activation. Blockage of this phosphorylation event prevents the separation of Daxx from Mdm2, stabilizes Mdm2, and inhibits DNA damage-induced p53 activation. These results suggest that phosphorylation of Daxx by ATM upon DNA damage disrupts the Daxx-Mdm2 interaction and facilitates p53 activation

Daxx is phosphorylated at Ser564 in response to DNA damage.

<p>(A) Flag-Daxx is phosphorylated upon DNA damage. p53-deficient H1299 cells were transiently transfected with Flag-tagged Daxx. 24 h later, the cells were treated with 10 μM etoposide (ETP) for the indicated durations. Cells were lysed and Flag-Daxx was immunoprecipitated with anti-Flag mAb (M2) beads and analyzed by western blot with antibodies against Daxx or phosphorylated ATM substrate consensus site (pS/T-Q). (B) Schematic representation of full length Daxx and its N-terminal deletion mutants. PAH, paired amphipathic alpha helices domain. AD, acidic-rich domain. SPT, Ser/Pro/Thr-rich domain. The amino acids in full length Daxx and in the N-terminus of each deletion mutant, and phosphorylation (Pi) of these mutants are indicated. (C) Phosphorylation of Daxx deletion mutants in response to DNA damage. H1299 cells expressing full-length (FL) Daxx and each of the deletion mutants were treated with ETP for 1 h. Phosphorylation of these proteins was analyzed as in (A). Exogenous Daxx phosphorylation existing before DNA damage was observed in some experiments, but not others. (D) Phosphorylation of Daxx at Ser564. Phosphorylation of Daxx, Daxx S424A, and Daxx S564A upon DNA damage was analyzed as in (c). (E) Alignment of the human Daxx (gi|48146287) sequence around Ser564 with the corresponding Daxx sequences from <i>Bos taurus</i> (gi|296474559), <i>Canis lupis familiaris</i> (gi|55956960), <i>Mus musculus</i> (gi|2253707), <i>Rattus norvegicus</i> (gi|18148939), <i>Salmo salar</i> (gi|148362139), and <i>Drosophila melanogaster</i> (gi|54144924). Alignment was run using Clustal 2.1 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055813#pone.0055813-Larkin1" target="_blank">[27]</a>.</p

Phosphorylation of Daxx at Ser564 regulates its interaction with Mdm2.

<p>(A) Daxx S564A has enhanced binding to Mdm2 upon DNA damage. H1299 cells were transfected with either HA-Daxx or HA-Daxx S564A alone, or together with Flag-Mdm2. Cells were treated with MG-132 (20 μM) for 4 h and ETP (20 μM) for the indicated times. Cell lysates were incubated with M2 beads. Input and immunoprecipitated proteins were analyzed by western blot. (B) HA-Mdm2 S395D was transfected alone and together with the indicated Flag-tagged Daxx plasmids into <i>p53-/- Mdm2-/-</i> MEFs. Cell lysates were incubated with M2 beads. The input lysates and immunoprecipitated proteins were analyzed by western blotting. (C) H1299 cells were transfected with HA-Mdm2 alone or together with Flag-Daxx or Flag-Daxx S564A. Cells were treated with CHX (50 μg/ml) for the indicated time periods and subjected to western blot analysis. Tubulin and co-transfected GFP are shown as controls for sample loading and transfection efficiency, respectively. (D) Daxx S564A can prolong the half-life of endogenous Mdm2. U2OS cells stably expressing Flag-Daxx or Flag-Daxx S564A were treated with CHX (20 μg/mL) for the indicated time. The expression of Daxx was detected separately by anti-Daxx and anti-Flag antibodies. (E) Daxx S564A can prolong the half-life of Mdm2 upon DNA damage. Flag-Mdm2 was transfected alone or together with the indicated HA-tagged Daxx plasmids into <i>p53-/- Mdm2-/-</i> MEFs. Cells were treated with ETP (20 μM) for 1 h prior to cycloheximide (CHX, 50 μg/ml) treatment for indicated time. GFP and actin are shown as controls for transfection and sample loading, respectively. (F) The effect of Daxx S564A on Mdm2 is dependent upon Hausp. Increasing amounts of Flag-Daxx S564A were transfected into U2OS cells treated with either control or Hausp siRNA and analyzed by western blot. Actin and GFP are shown as controls for sample loading and transfection efficiency, respectively. (G, H) Daxx S564A inhibits p53-mediated gene expression. MCF-7 (G) and U2OS (H) cells stably expressing Flag-Daxx or Flag-Daxx S564A were treated with 10 μM ETP for 8 h. Protein (G) and RNA (H) expression was analyzed by western blot and quantitative RT-PCR, respectively.</p

Daxx is phosphorylated by ATM <i>in vivo</i> and <i>in vitro</i>.

<p>(A) H1299 cells treated with a control (C) siRNA or ATM siRNA were transfected with Flag-Daxx and treated with etoposide. Cell lysates and immunoprecipitated Flag-Daxx were examined by western blot using anti-ATM, lamin A, anti-Daxx, and anti-pS/T-Q antibodies. (B) Phosphorylation of endogenous Daxx upon DNA damage in H1299 cells treated with ATM siRNA or control siRNA. (C) ATM phosphorylates Daxx at Ser564 <i>in vitro.</i> Top two panels: phosphorylated Daxx was detected by autoradiography (³²P-Daxx) and western blot (pS564-Daxx). Bottom two panels: input of ATM and Daxx proteins were analyzed by western blot and Coomassie Blue staining, respectively. (D) H1299 cells transfected with the GFP-Daxx were untreated (0) or treated with ETP for 1 or 4 h. Endogenous PML was detected by anti-PML antibody and Texas Red-labeled secondary antibody. Images were captured using confocal microscopy. (E) H1299 cells were transfected with Flag-Daxx or Flag-Daxx S564A. Cells were stained with anti-Flag and anti-PML antibodies.</p

Phosphorylation of endogenous Daxx upon DNA damage.

<p>(A) U2OS cells were transfected with control or Daxx siRNA and treated with ETP for 1 h. Cell lysates were analyzed by western blot using phospho-specific Daxx antibody, pS564-Daxx. (B) Phosphorylation of endogenous Daxx in multiple cell lines treated with and without etoposide for 1 h. Cell lysates were analyzed using antibodies against pS564-Daxx, Daxx, p53, and actin. (C) Western blot analysis of H1299 cells transfected with wild-type (WT) Daxx, Daxx S564A, or Daxx S424A and treated with ETP for 1 h. (D and E) U2OS (D) and H1299 (E) cells treated with ETP for the indicated time periods were analyzed by western blot. (F) H1299 cells were exposed to 10 Gy of ionizing radiation (IR) and cultured for the indicated time periods before analysis of Daxx phosphorylation.</p