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2 edition of SUMO-1 dependent and independent mechanisms of PML body assembly and disassembly. found in the catalog.

SUMO-1 dependent and independent mechanisms of PML body assembly and disassembly.

Christopher H. Eskiw

SUMO-1 dependent and independent mechanisms of PML body assembly and disassembly.

by Christopher H. Eskiw

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Published .
Written in English


About the Edition

Numerous discrete domains called nuclear bodies exist within the mammalian nucleus, which exhibit dynamic properties and are hypothesized to have critical roles in normal cellular function. Little is known about the mechanisms governing the formation and stability of nuclear bodies. Here, we used promyelocytic leukemia (PML) body as a paradigm to study the assembly/disassembly and stability of nuclear domains. Our aims included the analysis of underlying cause(s) for PML positional stability and to determine if chromatin contacts were influencing PML body integrity. We used environmental stresses (heat shock and heavy metal shock) to determine that PML bodies dissociate as supra-molecular complexes. We termed these small PML-containing structures, which lack PML-associated proteins as microstructures. These components were dynamic and moved by constrained diffusion. Ultrastructural analysis indicated that the mobility of microstructures was due to a lack of functional contact with other nucleoplasmic structures. During recovery from stress, microstructures fused with each other and parental PML bodies, coincident with increased levels of SUMO-1. During recovery, the position and the rank order size of PML bodies was conserved prior to and following recovery of cells from stress, indicating a non-random mechanism of PML body position and size conservation. Over-expression of SUMO-1 prevented the stress-mediated breakdown of PML bodies, indicating that PML body stability is partially dependent on SUMO-1. Direct transcriptional repression of cells by pharmaceutical agents also caused PML bodies to dissociate into supra-molecular complexes containing PML protein. These structures, however, contained detectable levels of SUMO-1. PML body breakdown was also observed in cells undergoing chromatin condensation as a result of chromatin cleavage, either in the early stages of apoptosis or by direct digestion by DNasel. Over-expression of SUMO-1 did not protect PML bodies from dissociating under these conditions, indicating that a second mechanism, independent of SUMO-1, is involved in PML body stability through PML interactions with the surrounding chromatin. Together, these finding indicate that both post-translational modification and the surrounding chromatin are involved in PML body assembly/disassembly and the maintenance of PML body integrity and may provide information to the formation, positional stability and dynamics of other nuclear bodies.

The Physical Object
Pagination220 leaves.
Number of Pages220
ID Numbers
Open LibraryOL19475337M
ISBN 100494026324

Promyelocytic leukemia protein is the protein product of the PML gene. PML protein is a tumor suppressor protein required for the assembly of a number of nuclear structures, called PML-nuclear bodies, which form amongst the chromatin of the cell nucleus. These nuclear bodies are present in mammalian nuclei, at about 1 to 30 per cell nucleus. PML-NBs are known to have a number of Aliases: PML, MYL, PP, RNF71, TRIM19, .   Enzymology and Regulation of SUMO Conjugation and Deconjugation. Three different ubiquitous SUMO-related proteins have been identified in mammalian cells, SUMO-1, SUMO-2, and SUMO-3, with SUMO-2 and SUMO-3 having greater sequence relatedness with each other than with SUMO-1 (3, 4).Recently a tissue-specific SUMO-4 has been identified in human kidney with homology .

Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions.   Altogether, these results suggest that PML NBs play an active role in enhancing gene repression by working as an assembly factory for Daxx-containing SUMOdependent co-repressor complexes. PML NBs may represent important cellular nodes for DNA repair or recombination since many forms of genotoxic stress increase their number.

  The assembly and disassembly of PML bodies (or ND10) at herpesvirus replication complexes are SUMO-dependent. Condensation of viral chromatin to achieve a latent, heterochromatin state is likely to be facilitated by sumoylation (48), and the reverse is true for reactivation.   The alternative lengthening of telomeres (ALT) mechanism allows cancer cells to escape senescence and apoptosis in the absence of active telomerase. A characteristic feature of this pathway is the assembly of ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs) at telomeres. Here, we dissected the role of APBs in a human ALT cell line by performing an RNA interference Cited by:


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SUMO-1 dependent and independent mechanisms of PML body assembly and disassembly by Christopher H. Eskiw Download PDF EPUB FB2

PML nuclear bodies (NBs) are nuclear structures that have been implicated in processes such as transcriptional regulation, genome stability, response to viral infection, apoptosis, and tumor suppression.

PML has been found to be essential for the formation of the NBs, as these structures do not form in Pml null cells Cited by:   PML has been found to be essential for the formation of the NBs, as these structures do not form in Pml null cells, while PML add back fully rescues their formation.

However, the basis for such a structural role of PML is by:   Not only do chromosomes occupy distinct, non-random territories, but many proteins that function in gene expression, DNA repair or RNA biogenesis are also stably compartmentalized or at least transit in distinct microenvironments called nuclear bodies.

1,2 The latter may enhance kinetics of enzymatic reactions in the nucleus that is otherwise devoid of membranes. 3,4 This nuclear Cited by: Overexpression of SUMO-1, a modification required for PML body formation, did not prevent PML body fission, indicating that chromatin-based integrity of PML body structure occurs through a SUMO SUMO-1, Sp and Daxx proteins are some of the core residents of the typical PML NB.

It is important to note that SUMO-1 modification and association with Sp seem to regulate the protein. in this issue of Molecular Cell), it is possible that these proteins are recruited to the PML networks to eventually form a higher order of protein structures such as the PML NB through noncovalent interactions mediated by covalently bound SUMO and SUMO binding motifs present in PML and these other NB components.

In agreement with this model and with the essential roles for PML SUMOylation and subsequent noncovalent binding through the SUMO binding motif Cited by:   PIAS1 is an E3 SUMO ligase involved in various cellular processes. Here, the authors use quantitative proteomics to identify potential PIAS1 substrates in human cells and elucidate the biological Author: Chongyang Li, Francis P.

McManus, Cédric Plutoni, Cristina Mirela Pascariu, Trent Nelson, Lara Elis. The SUMO pathway. The process of activating and attaching a SUMO to substrates results in the formation of an isopeptide bond between the carboxy-terminal carboxyl group of the SUMO and an ε-amino group of a substrate acceptor Lys residue 1 – with many other ubiquitin and ubiquitin-like proteins (Ubl proteins), all eukaryotic SUMO proteins are translated as immature precursors that Cited by: Author summary Promyelocytic leukemia (PML) nuclear bodies (NBs) are often targeted and reorganized by DNA viruses to counteract their antiviral activity.

Human papillomavirus (HPV) also associates with PML NBs after infectious entry. While PML protein is required for nuclear retention and efficient transcription of incoming HPV genomes, Sp, another PML NB component, was identified as a Cited by: 5.

Nuclear Body Assembly. PML NB-dependent SUMOylation is known to impact upon a number of distinct pathways (Van Damme et al., ). R.D. EverettDNA viruses and viral proteins that interact with PML nuclear bodies.

Oncogene, 20 (49) (), pp. Google Scholar. PML−/− MEFs were cotransfected with EYFP-PML and DsRed-TRF1, and at 3 h after transfection one 3D image stack was taken each minute (0–3 and 9–12). The area in the circle points to a PML body separating from a telomere.

(C) NB4 cells were treated with arsenic trioxide for 8 h to initiate PML body assembly. PML nuclear bodies (NBs) are spheres of – µm in diameter found in most cell-lines and many tissues.

They belong to the nuclear matrix, an ill-defined super-structure of the nucleus proposed to anchor and regulate many nuclear functions, including DNA replication, transcription, or epigenetic silencing (Stuurman et al.

The PML Cited by:   In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR.

Indeed, the PML protein itself contains both a SIM and at least three potential SUMOylation sites, and is thought to be the main protein responsible for protein recruitment to nuclear PML bodies.

It has also been proposed that PML body self-assembly is mediated by PML through intermolecular SUMO-SIM : Anna Lång, Emma Lång, Stig Ove Bøe. Although RanBP2 can accelerate the conjugation of both SUMO-1 and SUMO-2/3 to some substrates, it preferentially modifies PML, with SUMO-2 (Tatham et al., ).

Within the domain of RanBP2 that retains SUMO E3 ligase activity are two approximately residue repeated sequences (IR1 and IR2) separated by a short spacer region (M) (Saitoh et al Cited by: SUMO proteins are a family of conserved eukaryotic protein modifiers of approximately amino acids.

SUMO conjugation to the lysine(s) of substrates is carried out by SUMO E1, E2, and E3 enzymes (Johnson, ).Organisms examined so far contain only a single SUMO E1 and E2 enzyme but multiple SUMO E3 by: The small ubiquitin-like modifier (SUMO) is covalently linked to a variety of proteins and is deconjugated by SUMO-specific proteases.

A characteristic of SUMO modification is that the biological consequences of conjugation do not appear proportionate to the small fraction of substrate that is modified.

SUMO conjugation appears to alter the long-term fate of the modified protein even though Cited by: The small ubiquitin-like modifier (SUMO) is covalently attached to lysine residues in target proteins and in doing so changes the properties of the modified protein. Here we examine the role of SUMO modification in transcriptional by: PML and Sp proteins are covalently linked to SUMO-1, and ubiquitin-like peptide.

PML NBs are disorganized in acute promyelocytic leukemia and during several DNA virus infections. Dynamic SUMO conjugation and deconjugation of proteins exert a wide range of effects in biology.

Here, Zhao summarizes the current understanding of several mechanisms that underlie SUMO-mediated global effects on nuclear function and intracellular signaling to Cited by:. The promyelocytic leukemia (PML) gene is located on the long arm of chromosome 15 and was first described as part of a recurrent chromosomal translocation found in more than 95% of patients diagnosed with acute promyelocytic leukemia (APL) [1,2,3].It contains 9 exons and can be subjected to alternative mRNA splicing, leading to the expression of at least seven main PML : Anna Lång, Emma Lång, Stig Ove Bøe.

The promyelocytic leukemia (PML) protein has been implicated in many cellular pathways, but it is unclear whether the accumulation of PML and other proteins into PML nuclear bodies is a regulated or random process. In this paper we have used a variety of physiological stresses, including heat stress, Cd+2 exposure and adenovirus E1A expression, as tools to study the principles Cited by: Although recruitment of proteins through interferon-induced upregulation and SUMO-1 modification level of PML had been defined, it is not known whether release of proteins is regulated and has.