Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Electrospun poly(vinyl alcohol) nanofibers: effects of degree of hydrolysis and enhanced water stability

ArticlePOLYMER JOURNAL. 42(3):273-276 (2010)journal articl

Azimuthal anisotropy of K0S and Lambda + Lambda -bar production at midrapidity from Au+Au collisions at sqrt[sNN]=130 GeV

We report STAR results on the azimuthal anisotropy parameter v2 for strange particles K0S, Lambda , and Lambda -bar at midrapidity in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider. The value of v2 as a function of transverse momentum, pt, of the produced particle and collision centrality is presented for both particles up to pt~3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2 measurement is compared with hydrodynamic model calculations. The physics implications of the pt integrated v2 magnitude as a function of particle mass are also discussed.Alle Autoren: C. Adler, Z. Ahammed, C. Allgower, J. Amonett, B. D. Anderson, M. Anderson, G. S. Averichev, J. Balewski, O. Barannikova, L. S. Barnby, J. Baudot, S. Bekele, V. V. Belaga, R. Bellwied, J. Berger, H. Bichsel, A. Billmeier, L. C. Bland, C. O. Blyth, B. E. Bonner, A. Boucham, A. Brandin, A. Bravar, R. V. Cadman, H. Caines, M. Calderón de la Barca Sánchez, A. Cardenas, J. Carroll, J. Castillo, M. Castro, D. Cebra, P. Chaloupka, S. Chattopadhyay, Y. Chen, S. P. Chernenko, M. Cherney, A. Chikanian, B. Choi, W. Christie, J. P. Coffin, T. M. Cormier, J. G. Cramer, H. J. Crawford, W. S. Deng, A. A. Derevschikov, L. Didenko, T. Dietel, J. E. Draper, V. B. Dunin, J. C. Dunlop, V. Eckardt, L. G. Efimov, V. Emelianov, J. Engelage, G. Eppley, B. Erazmus, P. Fachini, V. Faine, K. Filimonov, E. Finch, Y. Fisyak, D. Flierl, K. J. Foley, J. Fu, C. A. Gagliardi, N. Gagunashvili, J. Gans, L. Gaudichet, M. Germain, F. Geurts, V. Ghazikhanian, O. Grachov, V. Grigoriev, M. Guedon, E. Gushin, T. J. Hallman, D. Hardtke, J. W. Harris, T. W. Henry, S. Heppelmann, T. Herston, B. Hippolyte, A. Hirsch, E. Hjort, G. W. Hoffmann, M. Horsley, H. Z. Huang, T. J. Humanic, G. Igo, A. Ishihara, Yu. I. Ivanshin, P. Jacobs, W. W. Jacobs, M. Janik, I. Johnson, P. G. Jones, E. G. Judd, M. Kaneta, M. Kaplan, D. Keane, J. Kiryluk, A. Kisiel, J. Klay, S. R. Klein, A. Klyachko, A. S. Konstantinov, M. Kopytine, L. Kotchenda, A. D. Kovalenko, M. Kramer, P. Kravtsov, K. Krueger, C. Kuhn, A. I. Kulikov, G. J. Kunde, C. L. Kunz, R. Kh. Kutuev, A. A. Kuznetsov, L. Lakehal-Ayat, M. A. C. Lamont, J. M. Landgraf, S. Lange, C. P. Lansdell, B. Lasiuk, F. Laue, A. Lebedev, R. Lednický, V. M. Leontiev, M. J. LeVine, Q. Li, S. J. Lindenbaum, M. A. Lisa, F. Liu, L. Liu, Z. Liu, Q. J. Liu, T. Ljubicic, W. J. Llope, G. LoCurto, H. Long, R. S. Longacre, M. Lopez-Noriega, W. A. Love, T. Ludlam, D. Lynn, J. Ma, R. Majka, S. Margetis, C. Markert, L. Martin, J. Marx, H. S. Matis, Yu. A. Matulenko, T. S. McShane, F. Meissner, Yu. Melnick, A. Meschanin, M. Messer, M. L. Miller, Z. Milosevich, N. G. Minaev, J. Mitchell, V. A. Moiseenko, C. F. Moore, V. Morozov, M. M. de Moura, M. G. Munhoz, J. M. Nelson, P. Nevski, V. A. Nikitin, L. V. Nogach, B. Norman, S. B. Nurushev, G. Odyniec, A. Ogawa, V. Okorokov, M. Oldenburg, D. Olson, G. Paic, S. U. Pandey, Y. Panebratsev, S. Y. Panitkin, A. I. Pavlinov, T. Pawlak, V. Perevoztchikov, W. Peryt, V. A Petrov, M. Planinic, J. Pluta, N. Porile, J. Porter, A. M. Poskanzer, E. Potrebenikova, D. Prindle, C. Pruneau, J. Putschke, G. Rai, G. Rakness, O. Ravel, R. L. Ray, S. V. Razin, D. Reichhold, J. G. Reid, F. Retiere, A. Ridiger, H. G. Ritter, J. B. Roberts, O. V. Rogachevski, J. L. Romero, A. Rose, C. Roy, V. Rykov, I. Sakrejda, S. Salur, J. Sandweiss, A. C. Saulys, I. Savin, J. Schambach, R. P. Scharenberg, N. Schmitz, L. S. Schroeder, A. Schüttauf, K. Schweda, J. Seger, D. Seliverstov, P. Seyboth, E. Shahaliev, K. E. Shestermanov, S. S. Shimanskii, V. S. Shvetcov, G. Skoro, N. Smirnov, R. Snellings, P. Sorensen, J. Sowinski, H. M. Spinka, B. Srivastava, E. J. Stephenson, R. Stock, A. Stolpovsky, M. Strikhanov, B. Stringfellow, C. Struck, A. A. P. Suaide, E. Sugarbaker, C. Suire, M. Šumbera, B. Surrow, T. J. M. Symons, A. Szanto de Toledo, P. Szarwas, A. Tai, J. Takahashi, A. H. Tang, J. H. Thomas, M. Thompson, V. Tikhomirov, M. Tokarev, M. B. Tonjes, T. A. Trainor, S. Trentalange, R. E. Tribble, V. Trofimov, O. Tsai, T. Ullrich, D. G. Underwood, G. Van Buren, A. M. VanderMolen, I. M. Vasilevski, A. N. Vasiliev, S. E. Vigdor, S. A. Voloshin, F. Wang, H. Ward, J. W. Watson, R. Wells, G. D. Westfall, C. Whitten, Jr., H. Wieman, R. Willson, S. W. Wissink, R. Witt, J. Wood, N. Xu, Z. Xu, A. E. Yakutin, E. Yamamoto, J. Yang, P. Yepes, V. I. Yurevich, Y. V. Zanevski, I. Zborovský, H. Zhang, W. M. Zhang, R. Zoulkarneev, and A. N. Zubarev (STAR Collaboration

Azimuthal anisotropy and correlations in the hard scattering regime at RHIC

Azimuthal anisotropy ($v_2$) and two-particle angular correlations of high $p_T$ charged hadrons have been measured in Au+Au collisions at $\sqrt{s_{NN}}$=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high $p_T$ partons. The monotonic rise of $v_2(p_T)$ for $p_T<2$ GeV/c is consistent with collective hydrodynamical flow calculations. At \pT>3 GeV/c a saturation of $v_2$ is observed which persists up to $p_T=6$ GeV/c.Comment: As publishe

Azimuthal anisotropy of K0s and Lambda prduction at mid-rapidity from Au+Au collisions at root s = 130 GeV

We report STAR results on the azimuthal anisotropy parameter v2 for strange particles K0S, L and Lbar at midrapidity in Au+Au collisions at sNN = 130 GeV at RHIC. The value of v2 as a function of transverse momentum of the produced particles pt and collision centrality is presented for both particles up to pt 3.0 GeV/c. A strong pt dependence in v2 is observed up to 2.0 GeV/c. The v2 measurement is compared with hydrodynamic model calculations. The physics implications of the pt integrated v2 magnitude as a function of particle mass are also discussed.Comment: 6 pages, 4 figures, by the STAR collaboratio

Disappearance of back-to-back high pTp_T hadron correlations in central Au+Au collisions at sNN\sqrt{s_{NN}} = 200 GeV

Azimuthal correlations for large transverse momentum charged hadrons have been measured over a wide pseudo-rapidity range and full azimuth in Au+Au and p+p collisions at $\sqrt{s_{NN}}$ = 200 GeV. The small-angle correlations observed in p+p collisions and at all centralities of Au+Au collisions are characteristic of hard-scattering processes already observed in elementary collisions. A strong back-to-back correlation exists for p+p and peripheral Au + Au. In contrast, the back-to-back correlations are reduced considerably in the most central Au+Au collisions, indicating substantial interaction as the hard-scattered partons or their fragmentation products traverse the medium.Comment: submitted to Phys. Rev. Let

Elliptic flow from two- and four-particle correlations in Au + Au collisions at sqrt{s_{NN}} = 130 GeV

Elliptic flow holds much promise for studying the early-time thermalization attained in ultrarelativistic nuclear collisions. Flow measurements also provide a means of distinguishing between hydrodynamic models and calculations which approach the low density (dilute gas) limit. Among the effects that can complicate the interpretation of elliptic flow measurements are azimuthal correlations that are unrelated to the reaction plane (non-flow correlations). Using data for Au + Au collisions at sqrt{s_{NN}} = 130 GeV from the STAR TPC, it is found that four-particle correlation analyses can reliably separate flow and non-flow correlation signals. The latter account for on average about 15% of the observed second-harmonic azimuthal correlation, with the largest relative contribution for the most peripheral and the most central collisions. The results are also corrected for the effect of flow variations within centrality bins. This effect is negligible for all but the most central bin, where the correction to the elliptic flow is about a factor of two. A simple new method for two-particle flow analysis based on scalar products is described. An analysis based on the distribution of the magnitude of the flow vector is also described.Comment: minor text change

Rapidity and centrality dependence of proton and antiproton production from 197Au + 197Au collisions at √SNN = 130 GeV

We report on the rapidity and centrality dependence of proton and antiproton transverse mass distributions from 197Au + 197Au collisions at sqrt[sNN ]=130 GeV as measured by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). Our results are from the rapidity and transverse momentum range of |y| <0.5 and 0.35< pt <1.00 GeV/c . For both protons and antiprotons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y| <0.5 . Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton (antiproton) yields and transverse mass distributions the possibility of prehadronic collective expansion may have to be taken into account

Pion-Xi correlations in Au-Au collisions at STAR

We present pion-Xi correlation analysis in Au-Au collisions at sqrt(s_NN)= 200 GeV and sqrt(s_NN) = 62.4 GeV, performed using the STAR detector at RHIC. A Xi*(1530) resonance signal is observed for the first time in Au-Au collisions. Experimental data are compared with theoretical predictions. The strength of the Xi* peak is reproduced in the correlation function assuming that pions and Xis emerge from a system in collective expansion.Comment: To appear in the proceedings of 18th Nuclear Physics Division Conference of the EPS (NPDC18),Prague, 23.8.-29.8. 200

RNA Is an Integral Component of Chromatin that Contributes to Its Structural Organization

Chromatin structure is influenced by multiples factors, such as pH, temperature, nature and concentration of counterions, post-translational modifications of histones and binding of structural non-histone proteins. RNA is also known to contribute to the regulation of chromatin structure as chromatin-induced gene silencing was shown to depend on the RNAi machinery in S. pombe, plants and Drosophila. Moreover, both in Drosophila and mammals, dosage compensation requires the contribution of specific non-coding RNAs. However, whether RNA itself plays a direct structural role in chromatin is not known. Here, we report results that indicate a general structural role for RNA in eukaryotic chromatin. RNA is found associated to purified chromatin prepared from chicken liver, or cultured Drosophila S2 cells, and treatment with RNase A alters the structural properties of chromatin. Our results indicate that chromatin-associated RNAs, which account for 2%–5% of total chromatin-associated nucleic acids, are polyA− and show a size similar to that of the DNA contained in the corresponding chromatin fragments. Chromatin-associated RNA(s) are not likely to correspond to nascent transcripts as they are also found bound to chromatin when cells are treated with α-amanitin. After treatment with RNase A, chromatin fragments of molecular weight >3.000 bp of DNA showed reduced sedimentation through sucrose gradients and increased sensitivity to micrococcal nuclease digestion. This structural transition, which is observed both at euchromatic and heterochromatic regions, proceeds without loss of histone H1 or any significant change in core-histone composition and integrity