共查询到20条相似文献,搜索用时 31 毫秒
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Alemu EA Sjøttem E Outzen H Larsen KB Holm T Bjørkøy G Johansen T 《Cellular and molecular life sciences : CMLS》2011,68(11):1953-1968
The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies,
denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKCι/λ and PKCζ serve important roles during development and
in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an
effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain
of PKCι/λ as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKCι/λ.
We confirmed the interaction of both aPKCs with TIEG1 in vitro and in cells, and found that both aPKCs phosphorylate the DNA-binding
domain of TIEG1 on two critical residues. Interestingly, the aPKC-mediated phosphorylation of TIEG1 affected its DNA-binding
activity, subnuclear localization and transactivation potential. 相似文献
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Poeschla EM 《Cellular and molecular life sciences : CMLS》2008,65(9):1403-1424
HIV integrates a DNA copy of its genome into a host cell chromosome in each replication cycle. The essential DNA cleaving
and joining chemistry of integration is known, but there is less understanding of the process as it occurs in a cell, where
two complex and dynamic macromolecular entities are joined: the viral pre-integration complex and chromatin. Among implicated
cellular factors, much recent attention has coalesced around LEDGF/p75, a nuclear protein that may act as a chromatin docking
factor or receptor for lentiviral pre-integration complexes. LEDGF/p75 tethers HIV integrase to chromatin, protects it from
degradation, and strongly influences the genome-wide pattern of HIV integration. Depleting the protein from cells and/or over-expressing
its integrase-binding domain blocks viral replication. Current goals are to establish the underlying mechanisms and to determine
whether this knowledge can be exploited for antiviral therapy or for targeting lentiviral vector integration in human gene
therapy.
Received 25 November 2007; received after revision 7 January 2008; accepted 10 January 2008 相似文献
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The inner nuclear membrane harbors a unique set of membrane proteins, many of which interact with nuclear intermediate filaments and chromatin components and thus play an important role in nuclear organization and gene expression regulation. These membrane proteins have to be constantly transported into the nucleus from their sites of synthesis in the ER to match the growth of the nuclear membrane during interphase. Many mechanisms have evolved to enable translocation of these proteins to the nucleus. The full range of mechanisms goes from rare autophagy events to regulated translocation using the nuclear pore complexes. Though mechanisms involving nuclear pores are predominant, within this group an enormous mechanistic range is observed from free diffusion through the peripheral channels to many distinct mechanisms involving different nucleoporins and other components of the soluble protein transport machinery in the central channels. This review aims to provide a comprehensive insight into this mechanistic diversity. 相似文献
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Santoro R 《Cellular and molecular life sciences : CMLS》2005,62(18):2067-2079
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Inositol pyrophosphates: structure, enzymology and function 总被引:2,自引:0,他引:2
Christopher John Barker Christopher Illies Gian Carlo Gaboardi Per-Olof Berggren 《Cellular and molecular life sciences : CMLS》2009,66(24):3851-3871
The stereochemistry of the inositol backbone provides a platform on which to generate a vast array of distinct molecular motifs that are used to convey information both in signal transduction and many other critical areas of cell biology. Diphosphoinositol phosphates, or inositol pyrophosphates, are the most recently characterized members of the inositide family. They represent a new frontier with both novel targets within the cell and novel modes of action. This includes the proposed pyrophosphorylation of a unique subset of proteins. We review recent insights into the structures of these molecules and the properties of the enzymes which regulate their concentration. These enzymes also act independently of their catalytic activity via protein–protein interactions. This unique combination of enzymes and products has an important role in diverse cellular processes including vesicle trafficking, endo- and exocytosis, apoptosis, telomere length regulation, chromatin hyperrecombination, the response to osmotic stress, and elements of nucleolar function. 相似文献
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Ignacio Campillo-Marcos Pedro A. Lazo 《Cellular and molecular life sciences : CMLS》2018,75(13):2375-2388
DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). This initiating kinase must be located in chromatin, and be activated independently of the type of DNA damage. We review the contribution of the Ser-Thr vaccinia-related kinase 1 (VRK1) chromatin kinase as a new player in the signaling of DNA damage responses, at chromatin and cellular levels, and its potential as a new therapeutic target in oncology. VRK1 is involved in the regulation of histone modifications, such as histone phosphorylation and acetylation, and in the formation of γH2AX, NBS1 and 53BP1 foci induced in DDR. Induction of DNA damage by chemotherapy or radiation is a mainstay of cancer treatment. Therefore, novel treatments can be targeted to proteins implicated in the regulation of DDR, rather than by directly causing DNA damage. 相似文献
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Reichert N Choukrallah MA Matthias P 《Cellular and molecular life sciences : CMLS》2012,69(13):2173-2187
Class I Histone deacetylases (HDACs) play a central role in controlling cell cycle regulation, cell differentiation, and tissue development. These enzymes exert their function by deacetylating histones and a growing number of non-histone proteins, thereby regulating gene expression and several other cellular processes. Class I HDACs comprise four members: HDAC1, 2, 3, and 8. Deletion and/or overexpression of these enzymes in mammalian systems has provided important insights about their functions and mechanisms of action which are reviewed here. In particular, unique as well as redundant functions have been identified in several paradigms. Studies with small molecule inhibitors of HDACs have demonstrated the medical relevance of these enzymes and their potential as therapeutic targets in cancer and other pathological conditions. Going forward, better understanding the specific role of individual HDACs in normal physiology as well as in pathological settings will be crucial to exploit this protein family as a useful therapeutic target in a range of diseases. Further dissection of the pathways they impinge on and of their targets, in chromatin or otherwise, will form important avenues of research for the future. 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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Massicotte G 《Cellular and molecular life sciences : CMLS》2000,57(11):1542-1550
Long-term potentiation (LTP) and long-term depression (LTD) are two electrophysiological models that have been studied extensively in recent years as they may represent basic mechanisms in many neuronal networks to store certain types of information. In several brain regions, it has been shown that these two forms of synaptic plasticity require sufficient dendritic depolarization, with the amplitude of the calcium signal being crucial for the generation of either LTP or LTD. The rise in calcium concentration mediated by the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to stimulate various calcium-dependent enzymatic processes that could convert the induction signal into long-lasting changes in synaptic structure; protein kinases and phosphatases have so far been considered predominantly with regard to LTP and LTD formation. According to several lines of experimental evidence, changes in synaptic function observed with LTP and LTD are thought to be the result of modifications of postsynaptic currents mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of glutamate receptors. Moreover, it has become apparent recently that activation of the calcium-dependent enzyme phospholipase A2 (PLA2) could be part of the molecular mechanisms involved in alterations of AMPA receptor properties during long-term changes in synaptic operation. In the present review, we will first describe the results that indicate a critical role of the phospholipases in regulating synaptic function. Next, sections will be devoted to the effects of PLA2 and phospholipids on the binding properties of glutamate receptors, and a revised biochemical model will be presented as an attempt to integrate the PLA2 enzyme into the mechanisms ( in particular kinases and phosphatases) that participate in adaptive neural plasticity. Finally, we will review data relevant to the issue of selective changes in AMPA binding after environmental enrichment and LTP. 相似文献
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Memory 总被引:2,自引:0,他引:2
In this review we address the idea that conservation of epigenetic mechanisms for information storage represents a unifying model in biology, with epigenetic mechanisms being utilized for cellular memory at levels from behavioral memory to development to cellular differentiation. Epigenetic mechanisms typically involve alterations in chromatin structure, which in turn regulate gene expression. An emerging idea is that the regulation of chromatin structure through histone acetylation and DNA methylation may mediate long-lasting behavioral change in the context of learning and memory. We find this idea fascinating because similar mechanisms are used for triggering and storing long-term 'memory' at the cellular level, for example when cells differentiate. An additional intriguing aspect of the hypothesis of a role for epigenetic mechanisms in information storage is that lifelong behavioral memory storage may involve lasting changes in the physical, three-dimensional structure of DNA itself. 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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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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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