A novel regulator of the p53-mediated mitochondrial apoptotic pathway

The p53 tumor suppressor protein induces apoptosis in response to genotoxic and environmental stress. Recent studies have revealed the existence of a transcription-independent mitochondrial p53 apoptosis pathway, however the mechanism regulating p53 translocation to mitochondria and subsequent initiation of apoptosis was not known. Here, we show that Tid1, also known as mtHsp40 or Dnaja3, interacts with p53 and directs its translocation to mitochondria in cells exposed to hypoxia. Overexpression of Tid1 in tumor cells promoted mitochondrial localization of both wildtype and mutant forms of p53 and was able to restore the pro-apoptotic activity of mutant p53 proteins that were otherwise unable to induce apoptosis. Tid1's mitochondrial signal sequence and DnaJ domain were both required for the movement of the p53-Tid1 complex from the cytosol to the mitochondria. Our findings establish Tid1 as a novel regulator of p53 localization and apoptotic function

Oxidization without substrate unfolding triggers proteolysis of the peroxide-sensor, PerR

Peroxide operon regulator (PerR) is a broadly conserved hydrogen peroxide sensor in bacteria, and oxidation of PerR at its regulatory metal-binding site is considered irreversible. Here, we tested whether this oxidation specifically targets PerR for proteolysis. We find that oxidizing conditions stimulate PerR degradation in vivo, and LonA is the principal AAA+ (ATPases associated with diverse cellular activities) protease that degrades PerR. Degradation of PerR by LonA is recapitulated in vitro, and biochemical dissection of this degradation reveals that the presence of regulatory metal and PerR-binding DNA dramatically extends the half-life of the protein. We identified a LonA-recognition site critical for oxidation-controlled PerR turnover. Key residues for LonA-interaction are exposed to solvent in PerR lacking metal, but are buried in the metal-bound form. Furthermore, one residue critical for Lon recognition is also essential for specific DNA-binding by PerR, thus explaining how both the metal and DNA ligands prevent PerR degradation. This ligand-controlled allosteric mechanism for protease recognition provides a compelling explanation for how the oxidation-induced conformational change in PerR triggers degradation. Interestingly, the critical residues recognized by LonA and exposed by oxidation do not function as a degron, because they are not sufficient to convert a nonsubstrate protein into a LonA substrate. Rather, these residues are a conformation-discriminator sequence, which must work together with other residues in PerR to evoke efficient degradation. This mechanism provides a useful example of how other proteins with only mild or localized oxidative damage can be targeted for degradation without the need for extensive oxidation-dependent protein denaturation.United States. Public Health Service (GM049224

Supersymmetric Gauge Theories with Flavors and Matrix Models

We present two results concerning the relation between poles and cuts by using the example of N=1 U(N_c) gauge theories with matter fields in the adjoint, fundamental and anti-fundamental representations. The first result is the on-shell possibility of poles, which are associated with flavors and on the second sheet of the Riemann surface, passing through the branch cut and getting to the first sheet. The second result is the generalization of hep-th/0311181 (Intriligator, Kraus, Ryzhov, Shigemori, and Vafa) to include flavors. We clarify when there are closed cuts and how to reproduce the results of the strong coupling analysis by matrix model, by setting the glueball field to zero from the beginning. We also make remarks on the possible stringy explanations of the results and on generalization to SO(N_c) and USp(2N_c) gauge groups.Comment: 52 pages, 6 figure

Recent Application of Bio-Alcohol: Bio-Jet Fuel

Recently, the biomass-based energy production has been actively studied as a research and development area for reducing carbon emissions as a solution to global warming caused by the increase of carbon dioxide emissions. Especially, as the energy consumption in the air transportation field increases, the carbon dioxide emissions increase simultaneously. Therefore, the bio-jet fuel production technology is being actively developed to solve this problem. The bio-jet fuel manufacturing process is a process of manufacturing biomass-derived jet fuel that can replace the existing petroleum-based jet fuel. It includes an alcohol-to-jet (ATJ) process using bio-alcohol such as bio-butanol and bio-ethanol, oil-to-jet (OTJ) process using vegetable oil, and an F-T process using syngas obtained from gasification of biomass-based raw materials

Note on Seiberg Duality in Matrix Model

In this note, we give a method to derive the Seiberg duality by the matrix model. The key fact we used is that the effective actions given by matrix model method should be identical for both electric and magnetic theories. We demonstrate our method for SQCD with U(N), SO(N) and Sp(N) gauge groups.Comment: 10 page

A New Parametrization of the Neutrino Mixing Matrix

The neutrino mixing matrix is expanded in powers of a small parameter $\lambda$, which approximately equals to 0.1. The meaning of every order of the expansion is discussed respectively, and the range of $\lambda$ is carefully calculated. We also present some applications of this new parametrization, such as to the expression of the Jarlskog parameter $J$, in which the simplicities and advantages of this parametrization are shown.Comment: 11 pages, 4 figures, version published in PL

Phases of N=1 USp(2N_c) Gauge Theories with Flavors

We studied the phase structures of N=1 supersymmetric USp(2N_c) gauge theory with N_f flavors in the fundamental representation as we deformed the N=2 supersymmetric QCD by adding the superpotential for adjoint chiral scalar field. We determined the most general factorization curves for various breaking patterns, for example, the two different breaking patterns of quartic superpotential. We observed all kinds of smooth transitions for quartic superpotential. Finally we discuss the intriguing role of USp(0) in the phase structure and the possible connection with observations made recently in hep-th/0304271 (Aganagic, Intriligator, Vafa and Warner) and in hep-th/0307063 (Cachazo).Comment: 61pp; Improved the presentation, references are added and to appear in PR

Estimate of neutrino masses from Koide's relation

We apply Koide's mass relation of charged leptons to neutrinos and quarks, with both the normal and inverted mass schemes of neutrinos discussed. We introduce the parameters $k_{\nu}$, $k_u$ and $k_d$ to describe the deviations of neutrinos and quarks from Koide's relation, and suggest a quark-lepton complementarity of masses such as $k_{l}+k_{d} \approx k_{\nu}+k_{u} \approx 2$. The masses of neutrinos are determined from the improved relation, and they are strongly hierarchical (with the different orders of magnitude of $10^{-5} eV$, $10^{-3} eV$, and $10^{-2} eV$).Comment: 12 latex pages, 4 figures, version in publicatio