246 results found
Batty E, Jensen K, Freemont P, 2009, PML nuclear bodies and their spatial relationships in the mammalian cell nucleus., Front Biosci (Landmark Ed), Vol: 14, Pages: 1182-1196
Promyelocytic leukaemia nuclear bodies (PML NBs) are found within the nucleus of mammalian cells, and are formed from the constituent proteins PML and Sp100. Numbering between 10 and 30 per cell, they are an obvious feature of the nuclear landscape, yet their functions have still to be unambiguously defined. In the mammalian nucleus, compartmentalization of functions is apparent, as reflected in the wide-range of other nuclear compartments that can be identified. These include nucleoli, transcription foci, splicing speckles, chromosomal topological markers such as centromeres and telomeres, the nuclear boundary, and the nucleoplasm itself. Quantification of the otherwise qualitative observations of relationships between mammalian nuclear compartments is essential for a complete understanding of nuclear processes. Here we describe some of the interesting known associations between PML NBs and other nuclear compartments, and comment upon their implications for PML NB function.
Batty E, Jensen K, Freemont P, 2009, PML nuclear bodies and their spatial relationships in the mammalian cell nucleus, FRONTIERS IN BIOSCIENCE-LANDMARK, Vol: 14, Pages: 1182-U7, ISSN: 1093-9946
Briggs LC, Baldwin GS, Miyata N, et al., 2008, Analysis of nucleotide binding to p97 reveals the properties of a tandem AAA hexameric ATPase, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 283, Pages: 13745-13752, ISSN: 0021-9258
Foerster A, Freemont PS, Mayer RJ, 2008, AAA proteins and the life process, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 36, Pages: 59-61, ISSN: 0300-5127
Yeung HO, Kloppsteck P, Niwa H, et al., 2008, Insights into adaptor binding to the AAA protein p97, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 36, Pages: 62-67, ISSN: 0300-5127
Poh J, Odendall C, Spanos A, et al., 2008, SteC is a Salmonella kinase required for SPI-2-dependent F-actin remodelling, Cellular Microbiology, Vol: 10, Pages: 20-30, ISSN: 1462-5814
Salmonella enterica serovar Typhimurium (S. Typhimurium) replicates inside mammalian cells within membrane‐bound compartments called Salmonella‐containing vacuoles. Intracellular replication is dependent on the activities of several effector proteins translocated across the vacuolar membrane by the Salmonella pathogenicity island 2 (SPI‐2)‐type III secretion system (T3SS). This is accompanied by the formation in the vicinity of bacterial vacuoles of an F‐actin meshwork, thought to be involved in maintaining the integrity of vacuolar membranes. In this study, we investigated the function of the SPI‐2 T3SS effector SteC. An steC mutant strain was not defective for intracellular replication or attenuated for virulence in mice. However, the steC mutant was defective for SPI‐2‐dependent F‐actin meshwork formation in host cells, although the vacuolar membranes surrounding mutant bacteria appeared to be normal. Expression of SteC in fibroblast cells following transfection caused extensive rearrangements of the F‐actin cytoskeleton. Sequence analysis identified amino acid similarity between SteC and the human kinase Raf‐1. A His‐tagged SteC fusion protein had kinase activity in vitro and a point mutant lacking kinase activity was unable to induce F‐actin rearrangements in vivo. We conclude that SPI‐2‐dependent F‐actin meshwork formation depends on the kinase activity of SteC, which resembles more closely eukaryotic than prokaryotic kinases.
Isaacson RL, Simpson PJ, Liu M, et al., 2007, A new labeling method for methyl transverse relaxation-optimized spectroscopy NMR spectra of alanine residues, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 129, Pages: 15428-+, ISSN: 0002-7863
p97 is an abundant, hexameric AAA ATPase, constituting 1% of the cytosol. It carries out diverse cellular roles, and is increasingly linked to ubiquitin in these processes. Ubiquitin modification determines the fate of many cellular proteins. Conjugation with a single ubiquitin molecule is a signal associated with altered protein trafficking whereas conjugation of a chain of ubiquitin can target a substrate protein to the proteasome for degradation, a function of the ubiquitin- proteasome system (UPS). Recent advances have established p97 (also known as VCP in mammals and Cdc48 in yeast) as a key part of the UPS, best characterized in the ERAD pathway. The UPS is a nonlysosomal proteolytic system, in which a candidate protein (short-lived or misfolded) is identified, modified with a ubiquitin chain, escorted to the proteasome and then unfolded, deubiquitinated and subjected to proteolysis. This involves recognition of the substrate protein and the actions of a succession of proteins on it. p97 is of particular importance as it is able to interact with many different proteins in this series of events. Current evidence points to a role for p97 in the identification and possible subsequent partial unfolding or disassembly of a given protein or protein complex. In the UPS, for example, this could be the disassembly of ubiquitinated proteins from unmodified proteins, prior to capture by the following interacting protein. It appears that this functionality possibly extends to other cellular processes that p97 participates in, such as post-mitotic membrane fusion. In this chapter we will give an overview of these p97 interacting proteins and detail how p97 targets ubiquitin-modified proteins in cellular processes such as ERAD. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.
Martin CA, Longman E, Wooding C, et al., 2007, Cd36, a class B scavenger receptor, functions as a monomer to bind acetylated and oxidized low-density lipoproteins, PROTEIN SCIENCE, Vol: 16, Pages: 2531-2541, ISSN: 0961-8368
Kitney RI, Freemont PS, Rouilly V, 2007, Engineering a molecular predation oscillator, IET Synthetic Biology, Vol: 1, Pages: 68-70, ISSN: 1752-1394
The paper addresses the problem of designing and building a stable molecular based oscillator which can be controlled in terms of both amplitude and frequency. A study of previous oscillators of this type showed that they are inherently unstable. To overcome this problem a design was chosen which is based on Lotka-Voltera dynamics. An important aspect of the work was the use of what we term the Engineering Cycle; that is, the cycle of system specification, design, modelling, implementation, and testing and validation. The Lotka-Voltera dynamic, in the context of a predation oscillator, amounts to a predator-prey approach. This is the basis of the oscillator design. The oscillator was designed and detailed modelling undertaken to establish the modes of the dynamic; how it could be tuned for stability; and how to control its amplitude and frequency. The biological implementation of the design was undertaken using a number of BioBricks from the MIT registry (http://parts.mit.edu/registry/ index.php/Main_Page), together with a number of parts which we designed and built. © 2007 The Institution of Engineering and Technology.
Shiels C, Adams NM, Islam SA, et al., 2007, Quantitative analysis of cell nucleus organisation, Plos Computational Biology, Vol: 3, Pages: 1161-1168, ISSN: 1553-7358
There are almost 1,300 entries for higher eukaryotes in the Nuclear Protein Database. The proteins' subcellular distribution patterns within interphase nuclei can be complex, ranging from diffuse to punctate or microspeckled, yet they all work together in a coordinated and controlled manner within the three-dimensional confines of the nuclear volume. In this review we describe recent advances in the use of quantitative methods to understand nuclear spatial organisation and discuss some of the practical applications resulting from this work.
Isaacson RL, Pye VE, Simpson P, et al., 2007, Detailed structural insights into the p97-Npl4-Ufd1 interface, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 282, Pages: 21361-21369, ISSN: 0021-9258
Barrett A, Santangelo S, Tan K, et al., 2007, Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases, INTERNATIONAL JOURNAL OF CANCER, Vol: 121, Pages: 265-275, ISSN: 0020-7136
Carpenter EP, Corbett A, Thomson H, et al., 2007, AP endonuclease paralogues with distinct activities in DNA repair and bacterial pathogenesis, EMBO JOURNAL, Vol: 26, Pages: 1363-1372, ISSN: 0261-4189
Rytkonen A, Poh J, Garmendia J, et al., 2007, SseL, a Salmonella deubiquitinase required for macrophage killing and virulence, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 104, Pages: 3502-3507, ISSN: 0027-8424
Muzzolini L, Beuron F, Patwardhan A, et al., 2007, Different quaternary structures of human RECQ1 are associated with its dual enzymatic activity, PLoS Biology, Vol: 5, Pages: 157-168, ISSN: 1544-9173
RecQ helicases are essential for the maintenance of chromosome stability. In addition to DNA unwinding, some RecQ enzymes have an intrinsic DNA strand annealing activity. The function of this dual enzymatic activity and the mechanism that regulates it is, however, unknown. Here, we describe two quaternary forms of the human RECQ1 helicase, higher-order oligomers consistent with pentamers or hexamers, and smaller oligomers consistent with monomers or dimers. Size exclusion chromatography and transmission electron microscopy show that the equilibrium between the two assembly states is affected by single-stranded DNA (ssDNA) and ATP binding, where ATP or ATPγS favors the smaller oligomeric form. Our three-dimensional electron microscopy reconstructions of human RECQ1 reveal a complex cage-like structure of approximately 120 Å × 130 Å with a central pore. This oligomeric structure is stabilized under conditions in which RECQ1 is proficient in strand annealing. In contrast, competition experiments with the ATPase-deficient K119R and E220Q mutants indicate that RECQ1 monomers, or tight binding dimers, are required for DNA unwinding. Collectively, our findings suggest that higher-order oligomers are associated with DNA strand annealing, and lower-order oligomers with DNA unwinding.
Pye VE, Beuron F, Keetch CA, et al., 2007, Structural insights into the p97-Ufd1-NpI4 complex, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 104, Pages: 467-472, ISSN: 0027-8424
Uchiyama K, Totsukawa G, Puhka M, et al., 2006, P37 is a p97 adaptor required for Golgi and ER biogenesis in interphase and at the end of mitosis, DEVELOPMENTAL CELL, Vol: 11, Pages: 803-816, ISSN: 1534-5807
McManus KJ, Stephens DA, Adams NM, et al., 2006, The transcriptional regulator CBP has defined spatial associations within interphase nuclei, PLOS COMPUTATIONAL BIOLOGY, Vol: 2, Pages: 1271-1283, ISSN: 1553-734X
Pye VE, Dreveny I, Briggs LC, et al., 2006, Going through the motions: The ATPase cycle of p97, JOURNAL OF STRUCTURAL BIOLOGY, Vol: 156, Pages: 12-28, ISSN: 1047-8477
Beuron F, Dreveny I, Yuan X, et al., 2006, Conformational changes in the AAA ATPase p97-p47 adaptor complex, Vol: 25, Pages: 1967-1976, ISSN: 0261-4189
Jensen K, Shiels C, Freemont PS, 2005, The ProMiscuousLy (PML) exciting nuclear protein has another partner - Comment, BLOOD, Vol: 105, Pages: 3393-3394, ISSN: 0006-4971
Madhusudan S, Smart F, Shrimpton P, et al., 2005, Isolation of a small molecule inhibitor of DNA base excision repair, NUCLEIC ACIDS RESEARCH, Vol: 33, Pages: 4711-4724, ISSN: 0305-1048
Dreveny I, Pye VE, Beuron F, et al., 2004, P97 and close encounters of every kind: a brief review, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 32, Pages: 715-720, ISSN: 0300-5127
Yuan XM, Simpson P, Mckeown C, et al., 2004, Structure, dynamics and interactions of p47, a major adaptor of the AAA ATPase, p97, EMBO JOURNAL, Vol: 23, Pages: 1463-1473, ISSN: 0261-4189
Borden KLB, Freemont PS, 2004, Introduction to supermolecular machines and assemblies, CURRENT PROTEIN & PEPTIDE SCIENCE, Vol: 5, ISSN: 1389-2037
Dreveny I, Kondo H, Uchiyama K, et al., 2004, Structural basis of the interaction between the AAA ATPase p97/VCP and its adaptor protein p47, EMBO JOURNAL, Vol: 23, Pages: 1030-1039, ISSN: 0261-4189
Yuan XM, Simpson P, Kondo H, et al., 2004, Letter to the Editor: Complete backbone resonance assignments of p47: The 41kDa adaptor protein of the AAA ATPase p97, JOURNAL OF BIOMOLECULAR NMR, Vol: 28, Pages: 309-310, ISSN: 0925-2738
Wang J, Shiels C, Sasieni P, et al., 2004, Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions, Journal of Cell Biology, Vol: 164, Pages: 515-526, ISSN: 0021-9525
The promyelocytic leukemia (PML) protein is aggregated into nuclear bodies that are associated with diverse nuclear processes. Here, we report that the distance between a locus and its nearest PML body correlates with the transcriptional activity and gene density around the locus. Genes on the active X chromosome are more significantly associated with PML bodies than their silenced homologues on the inactive X chromosome. We also found that a histone-encoding gene cluster, which is transcribed only in S-phase, is more strongly associated with PML bodies in S-phase than in G0/G1 phase of the cell cycle. However, visualization of specific RNA transcripts for several genes showed that PML bodies were not themselves sites of transcription for these genes. Furthermore, knock-down of PML bodies by RNA interference did not preferentially change the expression of genes closely associated with PML bodies. We propose that PML bodies form in nuclear compartments of high transcriptional activity, but they do not directly regulate transcription of genes in these compartments.
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