共查询到20条相似文献,搜索用时 78 毫秒
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Thomae AW Baltin J Pich D Deutsch MJ Ravasz M Zeller K Gossen M Hammerschmidt W Schepers A 《Cellular and molecular life sciences : CMLS》2011,68(22):3741-3756
In eukaryotes, binding of the six-subunit origin recognition complex (ORC) to DNA provides an interactive platform for the
sequential assembly of pre-replicative complexes. This process licenses replication origins competent for the subsequent initiation
step. Here, we analyze the contribution of human Orc6, the smallest subunit of ORC, to DNA binding and pre-replicative complex
formation. We show that Orc6 not only interacts with Orc1–Orc5 but also with the initiation factor Cdc6. Biochemical and imaging
experiments reveal that this interaction is required for licensing DNA replication competent. Furthermore, we demonstrate
that Orc6 contributes to the interaction of ORC with the chaperone protein HMGA1a (high mobility group protein A1a). Binding
of human ORC to replication origins is not specified at the level of DNA sequence and the functional organization of origins
is poorly understood. We have identified HMGA1a as one factor that might direct ORC to AT-rich heterochromatic regions. The
systematic analysis of the interaction between ORC and HMGA1a revealed that Orc6 interacts with the acidic C-terminus of HMGA1a
and also with its AT-hooks. Both domains support autonomous replication if targeted to DNA templates. As such, Orc6 functions
at different stages of the replication initiation process. Orc6 can interact with ORC chaperone proteins such as HMGA1a to
facilitate chromatin binding of ORC and is also an essential factor for pre-RC formation. 相似文献
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Chromatin assembly during S phase: contributions from histone deposition, DNA replication and the cell division cycle 总被引:7,自引:0,他引:7
During S phase of the eukaryotic cell division cycle, newly replicated DNA is rapidly assembled into chromatin. Newly synthesised
histones form complexes with chromatin assembly factors, mediating their deposition onto nascent DNA and their assembly into
nucleosomes. Chromatin assembly factor 1, CAF-1, is a specialised assembly factor that targets these histones to replicating
DNA by association with the replication fork associated protein, proliferating cell nuclear antigen, PCNA. Nucleosomes are
further organised into ordered arrays along the DNA by the activity of ATP-dependent chromatin assembly and spacing factors
such as ATP-utilising chromatin assembly and remodelling factor ACF. An additional level of controlling chromatin assembly
pathways has become apparent by the observation of functional requirements for cyclin-dependent protein kinases, casein kinase
II and protein phosphatases. In this review, we will discuss replication-associated histone deposition and nucleosome assembly
pathways, and we will focus in particular on how nucleosome assembly is linked to DNA replication and how it may be regulated
by the cell cycle control machinery. 相似文献
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T. Jenuwein G. Laible R. Dorn G. Reuter 《Cellular and molecular life sciences : CMLS》1998,54(1):80-93
The SET domain is a 130-amino acid, evolutionarily conserved sequence motif present in chromosomal proteins that function
in modulating gene activities from yeast to mammals. Initially identified as members of the Polycomb- and trithorax-group (Pc-G and trx-G) gene families, which are required to maintain expression boundaries of homeotic selector (HOM-C) genes,
SET domain proteins are also involved in position-effect-variegation (PEV), telomeric and centromeric gene silencing, and
possibly in determining chromosome architecture. These observations implicate SET domain proteins as multifunctional chromatin
regulators with activities in both eu- and heterochromatin – a role consistent with their modular structure, which combines
the SET domain with additional sequence motifs of either a cysteine-rich region/zinc-finger type or the chromo domain. Multiple
functions for chromatin regulators are not restricted to the SET protein family, since many trx-G (but only very few Pc-G)
genes are also modifiers of PEV. Together, these data establish a model in which the modulation of chromatin domains is mechanistically
linked with the regulation of key developmental loci (e.g. HOM-C). 相似文献
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Ismail Sahin Gul Paco Hulpiau Yvan Saeys Frans van Roy 《Cellular and molecular life sciences : CMLS》2017,74(3):525-541
The superfamily of armadillo repeat proteins is a fascinating archetype of modular-binding proteins involved in various fundamental cellular processes, including cell–cell adhesion, cytoskeletal organization, nuclear import, and molecular signaling. Despite their diverse functions, they all share tandem armadillo (ARM) repeats, which stack together to form a conserved three-dimensional structure. This superhelical armadillo structure enables them to interact with distinct partners by wrapping around them. Despite the important functional roles of this superfamily, a comprehensive analysis of the composition, classification, and phylogeny of this protein superfamily has not been reported. Furthermore, relatively little is known about a subset of ARM proteins, and some of the current annotations of armadillo repeats are incomplete or incorrect, often due to high similarity with HEAT repeats. We identified the entire armadillo repeat superfamily repertoire in the human genome, annotated each armadillo repeat, and performed an extensive evolutionary analysis of the armadillo repeat proteins in both metazoan and premetazoan species. Phylogenetic analyses of the superfamily classified them into several discrete branches with members showing significant sequence homology, and often also related functions. Interestingly, the phylogenetic structure of the superfamily revealed that about 30 % of the members predate metazoans and represent an ancient subset, which is gradually evolving to acquire complex and highly diverse functions. 相似文献
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Alternative splicing contributes greatly to proteomic complexity. How it is regulated by external stimuli to sculpt cellular properties, particularly the highly diverse and malleable neuronal properties, is an underdeveloped area of emerging interest. A number of recent studies in neurons and endocrine cells have begun to shed light on its regulation by calcium signals. Some mechanisms include changes in the trans-acting splicing factors by phosphorylation, protein level, alternative pre-mRNA splicing, and nucleocytoplasmic redistribution of proteins to alter protein–RNA or protein–protein interactions, as well as modulation of chromatin states. Importantly, functional analyses of the control of specific exons/splicing factors in the brain point to a crucial role of this regulation in synaptic maturation, maintenance, and transmission. Furthermore, its deregulation has been implicated in the pathogenesis of neurological disorders, particularly epilepsy/seizure. Together, these studies have not only provided mechanistic insights into the regulation of alternative splicing by calcium signaling but also demonstrated its impact on neuron differentiation, function, and disease. This may also help our understanding of similar regulations in other types of cells. 相似文献
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Kaser A Niederreiter L Blumberg RS 《Cellular and molecular life sciences : CMLS》2011,68(22):3643-3649
The intestinal epithelium forms a highly active functional interface between the relatively sterile internal body surfaces
and the enormously complex and diverse microbiota that are contained within the lumen. Genetic models that allow for manipulation
of genes specifically in the intestinal epithelium have provided an avenue to understand the diverse set of pathways whereby
intestinal epithelial cells (IECs) direct the immune state of the mucosa associated with homeostasis versus either productive
or non-productive inflammation as occurs during enteropathogen invasion or inflammatory bowel disease (IBD), respectively.
These pathways include the unfolded protein response (UPR) induced by stress in the endoplasmic reticulum (ER), autophagy,
a self-cannibalistic pathway important for intracellular bacterial killing and proper Paneth cell function as well as the
interrelated functions of NOD2/NF-κB signaling which also regulate autophagy induction. Multiple genes controlling these IEC
pathways have been shown to be genetic risk factors for human IBD. This highlights the importance of these pathways not only
for proper IEC function but also suggesting that IECs may be one of the cellular originators of organ-specific and systemic
inflammation as in IBD. 相似文献
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J. Mihaly I. Hogga S. Barges M. Galloni R. K. Mishra K. Hagstrom M. Müller P. Schedl L. Sipos J. Gausz H. Gyurkovics F. Karch 《Cellular and molecular life sciences : CMLS》1998,54(1):60-70
Eukaryotic chromosomes are thought to be organized into a series of discrete higher-order chromatin domains. This organization
is believed to be important not only in the compaction of the chromatin fibre, but also in the utilization of genetic information.
Critical to this model are the domain boundaries that delimit and segregate the chromosomes into units of independent gene
activity. In Drosophila, such domain boundaries have been identified through two different approaches. On the one hand, elements like scs/scs′ and
the reiterated binding site for the SU(HW) protein have been characterized through their activity of impeding enhancer-promoter
interactions when intercalated between them. Their role of chromatin insulators can protect transgenes from genomic position
effects, thereby establishing in dependent functional domains within the chromosome. On the other hand, domain boundaries
of the Bithorax complex (BX-C) like Fab-7 and Mcp have been identified through mutational analysis. Mcp and Fab-7, however, may represent a specific class of boundary elements; instead of separating adjacent domains that contain separate
structural genes, Mcp and Fab-7 delimit adjacent cis-regulatory domains, each of which interacts independently with their target promoters. In this article, we review the genetic
and molecular characteristics of the domain boundaries of the BX-C. We describe how Fab-7 functions to confine activating as well as repressive signals to the flanking regulatory domains. Although the mechanisms
by which Fab-7 works as a domain boundary remain an open issue, we provide preliminary evidence that Fab-7 is not a mere insulator like scs or the reiterated binding site for the SU(HW) protein. 相似文献
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Phylogenetic distribution, functional epitopes and evolution of the CSαβ superfamily 总被引:1,自引:1,他引:0
A superfamily of proteins often conserves a common structural scaffold but develops diverse biochemical and biological functions during evolution. The understanding of evolutionary mechanisms responsible for this diversity is of fundamental importance not only in structural genomics but also in nature-guided drug design. A superfamily of peptides with a conserved CSalphabeta structural motif provides a considerably intriguing example to approach such an issue. The peptides from this superfamily have wide origins, ranging from plants to animals, and exhibit diverse biological activities, varying from a sweet-tasting protein to antibacterial defensins and animal toxins targeting ion channels. This review describes the phylogenetic distribution and structural classifi cation of this unique scaffold and provides new insights into its functional diversity from the perspective of sequence, structure and evolution. 相似文献
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Bone morphogenetic proteins (BMPs) are one of the main classes of multi-faceted secreted factors that drive vertebrate development. A growing body of evidence indicates that BMPs contribute to the formation of the central nervous system throughout its development, from the initial shaping of the neural primordium to the generation and maturation of the different cell types that form the functional adult nervous tissue. In this review, we focus on the multiple activities of BMPs during spinal cord development, paying particular attention to recent results that highlight the complexity of BMP signaling during this process. These findings emphasize the unique capacity of these signals to mediate various functions in the same tissue throughout development, recruiting diverse effectors and strategies to instruct their target cells. 相似文献
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Of the numerous classes of elements involved in modulating eukaryotic chromosome structure and function, chromatin insulators arguably remain the most poorly understood in their contribution to these processes in vivo. Indeed, our view of chromatin insulators has evolved dramatically since their chromatin boundary and enhancer blocking properties were elucidated roughly a quarter of a century ago as a result of recent genome-wide, high-throughput methods better suited to probing the role of these elements in their native genomic contexts. The overall theme that has emerged from these studies is that chromatin insulators function as general facilitators of higher-order chromatin loop structures that exert both physical and functional constraints on the genome. In this review, we summarize the result of recent work that supports this idea as well as a number of other studies linking these elements to a diverse array of nuclear processes, suggesting that chromatin insulators exert master control over genome organization and behavior. 相似文献
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Polyamine-dependent gene expression 总被引:15,自引:0,他引:15
The polyamines spermidine and spermine along with the diamine putrescine are involved in
many cellular processes, including chromatin condensation, maintenance of DNA structure, RNA
processing, translation and protein activation. The polyamines influence the
formation of compacted chromatin and have a well-established role in DNA aggregation. Polyamines
are used in the posttranslational modification of eukaryotic initiation factor 5A, which regulates
the transport and processing of specific RNA. The polyamines also participate in a
novel RNA-decoding mechanism, a translational frameshift, of at least two known genes, the TY1
transposon and mammalian antizyme. Polyamines are crucial for their own regulation and are involved
in feedback mechanisms affecting both polyamine synthesis and catabolism. Recently, it has become
apparent that the polyamines are able to influence the action of the protein kinase
casein kinase 2. Here we address several roles of polyamines in gene expression.Received 27 November 2002; received after revision 9 January 2003; accepted 31 January 2003 相似文献
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Catherine Kirn-Safran Mary C. Farach-Carson Daniel D. Carson 《Cellular and molecular life sciences : CMLS》2009,66(21):3421-3434
Heparan sulfate proteoglycans are a remarkably diverse family of glycosaminoglycan-bearing protein cores that include the
syndecans, the glypicans, perlecan, agrin, and collagen XVIII. Members of this protein class play key roles during normal
processes that occur during development, tissue morphogenesis, and wound healing. As key components of basement membranes
in organs and tissues, they also participate in selective filtration of biological fluids, in establishing cellular barriers,
and in modulation of angiogenesis. The ability to perform these functions is provided both by the features of the protein
cores as well as by the unique properties of heparan sulfate, which is assembled as a polymer of N-acetylglucosamine and glucuronic acid and modified by specific enzymes to generate specialized biologically active structures.
This article discusses the structures and functions of this amazing family of proteoglycans and provides a platform for further
study of the individual members. 相似文献
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R. George H.-L. Chan Z. Ahmed K. M. Suen C. N. Stevens J. A. Levitt K. Suhling J. Timms J. E. Ladbury 《Cellular and molecular life sciences : CMLS》2009,66(4):711-720
The three isoforms of the adaptor protein Shc play diverse roles in cell signalling. For example, the observation of p46 Shc
in the nuclei of hepatocellular carcinoma cells suggests a function quite distinct from the better characterised cytoplasmic
role. Ligands responsible for the transport of various Shc isoforms into organelles such as the nucleus have yet to be reported.
To identify such ligands a far western approach was used to determine the p52 Shc interactome. The Ran-GTPase nuclear transport
protein was identified and found to bind to p52 Shc in vitro with low micromolar affinity. Co-immunoprecipitation, pull down and fluorescence lifetime imaging microscopy experiments
in stable cells confirmed cellular interaction and nuclear localisation. The nuclear transport factor protein NTF2, which
functions in cohort with Ran, was shown to form a complex with both RAN and Shc, suggesting a mechanism for Shc entry into
the nucleus as part of a tertiary complex.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 20 October 2008; received after revision 04 December 2008; accepted 15 December 2008 相似文献