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Dephosphorylation of DBC1 by Protein Phosphatase 4 Is Important for p53-Mediated Cellular Functions
이지혜,Guillaume Adelmant,Jarrod A. Marto,이동현 한국분자세포생물학회 2015 Molecules and cells Vol.38 No.8
Deleted in breast cancer-1 (DBC1) contributes to the regulation of cell survival and apoptosis. Recent studies demonstrated that DBC is phosphorylated at Thr454 by ATM/ATR kinases in response to DNA damage, which is a critical event for p53 activation and apoptosis. However, how DBC1 phosphorylation is regulated has not been studied. Here we show that protein phosphatase 4 (PP4) dephosphorylates DBC1, regulating its role in DNA damage response. PP4R2, a regulatory subunit of PP4, mediates the interaction between DBC1 and PP4C, a catalytic subunit. PP4C efficiently dephosphorylates pThr454 on DBC1 in vitro, and the depletion of PP4C/PP4R2 in cells alters the kinetics of DBC1 phosphorylation and p53 activation, and increases apoptosis in response to DNA damage, which are compatible with the expression of the phosphomimetic DBC-1 mutant (T454E). These suggest that the PP4-mediated dephosphorylation of DBC1 is necessary for efficient damage responses in cells.
Dephosphorylation of DBC1 by Protein Phosphatase 4 Is Important for p53-Mediated Cellular Functions
Lee, Jihye,Adelmant, Guillaume,Marto, Jarrod A.,Lee, Dong-Hyun Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.8
Deleted in breast cancer-1 (DBC1) contributes to the regulation of cell survival and apoptosis. Recent studies demonstrated that DBC is phosphorylated at Thr454 by ATM/ATR kinases in response to DNA damage, which is a critical event for p53 activation and apoptosis. However, how DBC1 phosphorylation is regulated has not been studied. Here we show that protein phosphatase 4 (PP4) dephosphorylates DBC1, regulating its role in DNA damage response. PP4R2, a regulatory subunit of PP4, mediates the interaction between DBC1 and PP4C, a catalytic subunit. PP4C efficiently dephosphorylates pThr454 on DBC1 in vitro, and the depletion of PP4C/PP4R2 in cells alters the kinetics of DBC1 phosphorylation and p53 activation, and increases apoptosis in response to DNA damage, which are compatible with the expression of the phosphomimetic DBC-1 mutant (T454E). These suggest that the PP4-mediated dephosphorylation of DBC1 is necessary for efficient damage responses in cells.
Dephosphorylation Enables the Recruitment of 53BP1 to Double-Strand DNA Breaks
Lee, D.H.,Acharya, Sanket S.,Kwon, M.,Drane, P.,Guan, Y.,Adelmant, G.,Kalev, P.,Shah, J.,Pellman, D.,Marto, Jarrod A.,Chowdhury, D. Cell Press 2014 Molecular cell Vol.54 No.3
Excluding 53BP1 from chromatin is required to attenuate the DNA damage response during mitosis, yet the functional relevance and regulation of this exclusion are unclear. Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif. Phosphorylating these sites blocks the interaction of the UDR motif with mononuclesomes containing ubiquitinated histone H2A and impedes binding of 53BP1 to mitotic chromatin. Ectopic recruitment of 53BP1-T1609A/S1618A to mitotic DNA lesions was associated with significant mitotic defects that could be reversed by inhibiting nonhomologous end-joining. We also reveal that protein phosphatase complex PP4C/R3β dephosphorylates T1609 and S1618 to allow the recruitment of 53BP1 to chromatin in G1 phase. Our results identify key sites of 53BP1 phosphorylation during mitosis, identify the counteracting phosphatase complex that restores the potential for DDR during interphase, and establish the physiological importance of this regulation.
Aad, G.,Abbott, B.,Abdallah, J.,Abdel Khalek, S.,Abdinov, O.,Aben, R.,Abi, B.,Abolins, M.,AbouZeid, O. S.,Abramowicz, H.,Abreu, H.,Abreu, R.,Abulaiti, Y.,Acharya, B. S.,Adamczyk, L.,Adams, D. L.,Adelm Springer Berlin Heidelberg 2014 European Physical Journal C Vol.74 No.8
<P>The integrated elliptic flow of charged particles produced in Pb+Pb collisions at [FORMULA OMISSION] TeV has been measured with the ATLAS detector using data collected at the Large Hadron Collider. The anisotropy parameter, [FORMULA OMISSION], was measured in the pseudorapidity range [FORMULA OMISSION] with the event-plane method. In order to include tracks with very low transverse momentum [FORMULA OMISSION], thus reducing the uncertainty in [FORMULA OMISSION] integrated over [FORMULA OMISSION], a [FORMULA OMISSION] data sample recorded without a magnetic field in the tracking detectors is used. The centrality dependence of the integrated [FORMULA OMISSION] is compared to other measurements obtained with higher [FORMULA OMISSION] thresholds. The integrated elliptic flow is weakly decreasing with [FORMULA OMISSION]. The integrated [FORMULA OMISSION] transformed to the rest frame of one of the colliding nuclei is compared to the lower-energy RHIC data.</P>
Aad, G.,Abbott, B.,Abdallah, J.,Abdel Khalek, S.,Abdinov, O.,Aben, R.,Abi, B.,Abolins, M.,AbouZeid, O. S.,Abramowicz, H.,Abreu, H.,Abreu, R.,Abulaiti, Y.,Acharya, B. S.,Adamczyk, L.,Adams, D. L.,Adelm Springer Berlin Heidelberg 2014 European Physical Journal C Vol.74 No.11
<P>Additional jet activity in dijet events is measured using [FORMULA OMISSION] collisions at ATLAS at a centre-of-mass energy of [FORMULA OMISSION], for jets reconstructed using the [FORMULA OMISSION] algorithm with radius parameter [FORMULA OMISSION]. This is done using variables such as the fraction of dijet events without an additional jet in the rapidity interval bounded by the dijet subsystem and correlations between the azimuthal angles of the dijet s. They are presented, both with and without a veto on additional jet activity in the rapidity interval, as a function of the scalar average of the transverse momenta of the dijet s and of the rapidity interval size. The double differential dijet cross section is also measured as a function of the interval size and the azimuthal angle between the dijet s. These variables probe differences in the approach to resummation of large logarithms when performing QCD calculations. The data are compared to <SMALL>POWHEG</SMALL>, interfaced to the <SMALL>PYTHIA</SMALL> 8 and <SMALL>HERWIG</SMALL> parton shower generators, as well as to <SMALL>HEJ</SMALL> with and without interfacing it to the <SMALL>ARIADNE</SMALL> parton shower generator. None of the theoretical predictions agree with the data across the full phase-space considered; however, <SMALL>POWHEG+PYTHIA</SMALL> 8 and <SMALL>HEJ</SMALL>+<SMALL>ARIADNE</SMALL> are found to provide the best agreement with the data. These measurements use the full data sample collected with the ATLAS detector in [FORMULA OMISSION][FORMULA OMISSION] collisions at the LHC and correspond to integrated luminosities of [FORMULA OMISSION] and [FORMULA OMISSION] for data collected during 2010 and 2011, respectively.</P>
Aad, G.,Abbott, B.,Abdallah, J.,Abdel Khalek, S.,Abdinov, O.,Aben, R.,Abi, B.,Abolins, M.,AbouZeid, O. S.,Abramowicz, H.,Abreu, H.,Abreu, R.,Abulaiti, Y.,Acharya, B. S.,Adamczyk, L.,Adams, D. L.,Adelm Springer Berlin Heidelberg 2014 European Physical Journal C Vol.74 No.12
<P>The ratio of the production cross sections for [FORMULA OMISSION] and [FORMULA OMISSION] bosons in association with jets has been measured in proton–proton collisions at [FORMULA OMISSION] with the ATLAS experiment at the Large Hadron Collider. The measurement is based on the entire 2011 dataset, corresponding to an integrated luminosity of [FORMULA OMISSION]. Inclusive and differential cross-section ratios for massive vector bosons decaying to electrons and muons are measured in association with jets with transverse momentum [FORMULA OMISSION] and jet rapidity [FORMULA OMISSION]. The measurements are compared to next-to-leading-order perturbative QCD calculations and to predictions from different Monte Carlo generators implementing leading-order matrix elements supplemented by parton showers.</P>
Aad, G.,Abbott, B.,Abdallah, J.,Khalek, S. Abdel,Abdinov, O.,Aben, R.,Abi, B.,Abolins, M.,AbouZeid, O. S.,Abramowicz, H.,Abreu, H.,Abreu, R.,Abulaiti, Y.,Acharya, B. S.,Adamczyk, L.,Adams, D. L.,Adelm Springer Berlin Heidelberg 2014 The European physical journal. C, Particles and fi Vol.74 No.6
<P>A search is presented for direct top squark pair production using events with at least two leptons including a same-flavour opposite-sign pair with invariant mass consistent with the [FORMULA OMISSION] boson mass, jets tagged as originating from [FORMULA OMISSION]-quarks and missing transverse momentum. The analysis is performed with proton–proton collision data at [FORMULA OMISSION] collected with the ATLAS detector at the LHC in 2012 corresponding to an integrated luminosity of 20.3 fb[FORMULA OMISSION]. No excess beyond the Standard Model expectation is observed. Interpretations of the results are provided in models based on the direct pair production of the heavier top squark state ([FORMULA OMISSION]) followed by the decay to the lighter top squark state ([FORMULA OMISSION]) via [FORMULA OMISSION], and for [FORMULA OMISSION] pair production in natural gauge-mediated supersymmetry breaking scenarios where the neutralino ([FORMULA OMISSION]) is the next-to-lightest supersymmetric particle and decays producing a [FORMULA OMISSION] boson and a gravitino ([FORMULA OMISSION]) via the [FORMULA OMISSION] process.</P>
Search for the lepton flavor violating decayZ→eμinppcollisions ats=8 TeVwith the ATLAS detector
Aad, G.,Abbott, B.,Abdallah, J.,Abdel Khalek, S.,Abdinov, O.,Aben, R.,Abi, B.,Abolins, M.,AbouZeid, O. S.,Abramowicz, H.,Abreu, H.,Abreu, R.,Abulaiti, Y.,Acharya, B. S.,Adamczyk, L.,Adams, D. L.,Adelm American Physical Society 2014 PHYSICAL REVIEW D - Vol.90 No.7
Aad, G.,Abbott, B.,Abdallah, J.,Abdel Khalek, S.,Abdinov, O.,Aben, R.,Abi, B.,Abolins, M.,AbouZeid, O. S.,Abramowicz, H.,Abreu, H.,Abreu, R.,Abulaiti, Y.,Acharya, B. S.,Adamczyk, L.,Adams, D. L.,Adelm Springer Berlin Heidelberg 2014 European Physical Journal C Vol.74 No.8
<P>A likelihood-based discriminant for the identification of quark- and gluon-initiated jets is built and validated using 4.7 fb[FORMULA OMISSION] of proton–proton collision data at [FORMULA OMISSION] [FORMULA OMISSION] collected with the ATLAS detector at the LHC. Data samples with enriched quark or gluon content are used in the construction and validation of templates of jet properties that are the input to the likelihood-based discriminant. The discriminating power of the jet tagger is established in both data and Monte Carlo samples within a systematic uncertainty of [FORMULA OMISSION] 10–20 %. In data, light-quark jets can be tagged with an efficiency of [FORMULA OMISSION] while achieving a gluon-jet mis-tag rate of [FORMULA OMISSION] in a [FORMULA OMISSION] range between [FORMULA OMISSION] and [FORMULA OMISSION] for jets in the acceptance of the tracker. The rejection of gluon-jets found in the data is significantly below what is attainable using a <SMALL>PYTHIA</SMALL> 6 Monte Carlo simulation, where gluon-jet mis-tag rates of 10 % can be reached for a 50 % selection efficiency of light-quark jets using the same jet properties.</P>