Abstract:
:A recent study has shown that the dimeric form of the 50-kD DNA-binding subunit of the NF-kappa B transcription factor is commonly associated with two molecules of a 65-kD protein (p65) and that p65 appears to be required for inactivation of the p50 dimer by the inhibitory subunit I kappa B. Here, we provide evidence that p65 serves as a receptor for I kappa B. Preincubation of I kappa B with purified p65 prevented I kappa B from inactivating the heterotetrameric form of NF-kappa B. Furthermore, excess p65 could very efficiently activate the latent form of NF-kappa B composed of p50, p65, and I kappa B, presumably by binding the I kappa B, which was released from the complex due to its inherent off rate. An additional function of p65 in modulating the DNA-binding specificity of p50 was found. In the absence of p65, p50 could bind with high affinity to completely palindromic sites. The heterotetramer recognized these sites with an affinity greater than 10-fold lower but preferred the less symmetric physiological kappa B site. The affinity of p50 for the most frequent kappa B motif 5'-GGGACTTTCC-3' was enhanced twofold by p65 to yield a dissociation constant of approximately 4 x 10(-13) M. This study describes novel functions for a non-DNA-binding accessory protein of a transcription factor in controlling its inducibility and DNA-binding specificity.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Urban MB,Baeuerle PAdoi
10.1101/gad.4.11.1975subject
Has Abstractpub_date
1990-11-01 00:00:00pages
1975-84issue
11eissn
0890-9369issn
1549-5477journal_volume
4pub_type
杂志文章abstract::Members of the metazoan nuclear receptor superfamily regulate gene expression programs in response to binding of cognate lipophilic ligands. Evolutionary studies using bioinformatics tools have concluded that lower eukaryotes, such as fungi, lack nuclear receptor homologs. Here we review recent discoveries suggesting ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1743009
更新日期:2009-02-15 00:00:00
abstract::The connection between RNA and protein export from the nucleus was examined in the budding yeast Saccharomyces cerevisiae. NPL3 encodes an RNA-binding protein that shuttles in and out of the nucleus. Export of poly(A)+ RNA has been shown previously to be blocked in np13-1 mutants. To understand the role of Np13p in RN...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.10.1233
更新日期:1996-05-15 00:00:00
abstract::The Dorsal morphogen is a transcription factor that activates some genes and represses others to establish multiple domains of gene expression along the dorsal/ventral axis of the early Drosophila embryo. Repression by Dorsal appears to require accessory proteins that bind to corepression elements in Dorsal-dependent ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.24.3177
更新日期:1995-12-15 00:00:00
abstract::Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potent...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.226837.113
更新日期:2013-11-15 00:00:00
abstract::Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell-specific deletion of Max has a modest effect on B-cell development but completely abrogates Eµ-Myc-driven lymphomagenesis. While Max loss affects only a few hund...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.325878.119
更新日期:2019-09-01 00:00:00
abstract::Maternal imprinting at the Xist gene is essential to achieve paternal allele-specific imprinted X-chromosome inactivation (XCI) in female mammals. However, the mechanism underlying Xist imprinting is unclear. Here we show that the Xist locus is coated with a broad H3K27me3 domain that is established during oocyte grow...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.304113.117
更新日期:2017-10-01 00:00:00
abstract::Cell differentiation is essential for the development of multicellular organisms. In flowering plants, the haploid male gametophytes (pollen grains) are generated in the anther from reproductive cells called microsporocytes. Several types of somatic cells ensure successful pollen development, and thus reproduction. Ho...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.997902
更新日期:2002-08-01 00:00:00
abstract::Adult mesenchymal stem cells (MSCs) derived from bone marrow contribute to the regeneration of multiple types of mesenchymal tissues. Here we describe the functional role of a novel form of cross-talk between the transforming growth factor beta1 (TGF-beta1) and Wnt signaling pathways in regulating the activities of hu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1388806
更新日期:2006-03-15 00:00:00
abstract::Treatment with retinoic acid (RA) is known to produce complex teratogenic effects in vertebrates, and its presence in the developing embryo as an endogenous substance has led to the suggestion that RA might be a natural morphogenetic agent. Although our understanding of the molecular mechanism of RA action has improve...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.8.1333
更新日期:1991-08-01 00:00:00
abstract::The release of Agrin by motoneurons activates the muscle-specific receptor tyrosine kinase (MuSK) as the main organizer of subsynaptic specializations at the neuromuscular junction. MuSK downstream signaling is largely undefined. Here we show that protein kinase CK2 interacts and colocalizes with MuSK at post-synaptic...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.375206
更新日期:2006-07-01 00:00:00
abstract::Cells have evolved checkpoint responses to arrest or delay the cell cycle, activate DNA repair networks, or induce apoptosis after genomic perturbation. Cells have also evolved the translesion synthesis processes to tolerate genomic lesions by either error-free or error-prone repair. Here, we show that after a replica...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1043203
更新日期:2003-01-01 00:00:00
abstract::The mouse Nedd5 gene encodes a 41.5-kD GTPase similar to the Saccharomyces and Drosophila septins essential for cytokinesis. Nedd5 accumulates near the contractile ring from anaphase through telophase, and finally condenses into the midbody. Microinjection of anti-Nedd5 antibody interferes with cytokinesis, giving ris...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.12.1535
更新日期:1997-06-15 00:00:00
abstract::Binding of microRNA (miRNA) to mRNA within the RNA-induced silencing complex (RISC) leads to either translational inhibition or to destruction of the target mRNA. Both of these functions are executed by Argonaute 2 (Ago2). Using hematopoiesis in mice as a model system to study the physiological function of Ago2 in viv...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1565607
更新日期:2007-08-15 00:00:00
abstract::Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the mol...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.207654.112
更新日期:2013-03-01 00:00:00
abstract::Many tumors continuously depend on the initiating oncogenes, but whether this extends to their downstream targets is unclear. In this issue of Genes & Development, Sodir and colleagues (pp. 907-916) demonstrate an essential role for endogenous Myc proteins in maintaining the tumor microenvironment, providing an unexpe...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.2053311
更新日期:2011-05-01 00:00:00
abstract::VASA is an evolutionarily conserved RNA helicase essential for germ cell development. The mouse PIWI family proteins MILI and MIWI2 are involved in production of Piwi-interacting RNAs (piRNAs) in fetal male germ cells through a ping-pong amplification cycle. Expression of retrotransposons is elevated in MILI- and MIWI...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1902110
更新日期:2010-05-01 00:00:00
abstract::To investigate the relationship between splicing and polyadenylation during the production of vertebrate mRNAs, we examined the effect of mutation of a poly(A) site on splicing of upstream introns. Mutation of the AAUAAA polyadenylation consensus sequence inhibited in vitro splicing of an upstream intron. The magnitud...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.11.2086
更新日期:1991-11-01 00:00:00
abstract::The generation of neurons by progenitor cells involves the tight coordination of multiple cellular activities, including cell cycle exit, initiation of neuronal differentiation, and cell migration. The mechanisms that integrate these different events into a coherent developmental program are not well understood. Here ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.377106
更新日期:2006-06-01 00:00:00
abstract::The Wnt signaling cascade is a central regulator of cell fate determination during embryonic development, whose deregulation contributes to oncogenesis. Naked cuticle is the first Wnt-induced antagonist found in this pathway, establishing a negative-feedback loop that limits the Wnt signal required for early segmentat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.328905
更新日期:2005-02-01 00:00:00
abstract::The abundance of retinoic acid (RA) is determined by the balance between its synthesis by retinaldehyde dehydrogenase (RALDH) and its degradation by CYP26. In particular, the dynamic expression of three CYP26 genes controls the regional level of RA within the body. Pregastrulation mouse embryos express CYP26 but not R...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1776209
更新日期:2009-07-15 00:00:00
abstract::Metastasis accounts for the vast majority of cancer-related deaths, yet the molecular mechanisms that drive metastatic spread remain poorly understood. Here we report that Tks5, which has been linked to the formation of proteolytic cellular protrusions known as invadopodia, undergoes an isoform switch during metastati...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.222745.113
更新日期:2013-07-15 00:00:00
abstract::We have compared the expression of the murine genes En-1,En-2, and in-1 during development by in situ hybridization. Expression of all three genes was first detected at 8.0 days in overlapping bands of the anterior neural folds. By 12.0 days the expression patterns diverged. En-1 and En-2 were expressed in a similar r...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.12b.1736
更新日期:1988-12-01 00:00:00
abstract::While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of mi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.303537.117
更新日期:2017-07-15 00:00:00
abstract::Organization into polarized three-dimensional structures defines whether epithelial cells are normal or malignant. In a model of morphogenesis, we show that inhibiting key signaling pathways in human breast cancer cells leads to "phenotypic reversion" of the malignant cells. Using architecture as an endpoint, we repor...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1990410
更新日期:2010-12-15 00:00:00
abstract::DOCK180 is involved in integrin signaling through CrkII-p130(Cas) complexes. We have studied the involvement of DOCK180 in Rac1 signaling cascades. DOCK180 activated JNK in a manner dependent on Rac1, Cdc42Hs, and SEK, and overexpression of DOCK180 increased the amount of GTP-bound Rac1 in 293T cells. Coexpression of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.21.3331
更新日期:1998-11-01 00:00:00
abstract::The formation of the apical ectodermal ridge (AER) is critical for the distal outgrowth and patterning of the vertebrate limb. Recent work in the chick has demonstrated that interplay between the Wnt and Fgf signaling pathways is essential in the limb mesenchyme and ectoderm in the establishment and perhaps the mainte...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1044903
更新日期:2003-02-01 00:00:00
abstract::Integrin-mediated cell-matrix interactions are essential for development, tissue homeostasis, and repair. Upon ligand binding, integrins are recruited into focal adhesions (FAs). Integrin-linked kinase (ILK) is an FA component that interacts with the cytoplasmic domains of integrins, recruits adaptor proteins that lin...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.255603
更新日期:2003-04-01 00:00:00
abstract::Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly understood within the local chromatin environment surrounding replicat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.247924.114
更新日期:2015-01-15 00:00:00
abstract::Genomic imprinting is an epigenetic mechanism by which genes are expressed in a parental origin-dependent manner. We recently discovered that, like DNA methylation, oocyte-inherited H3K27me3 can also serve as an imprinting mark in mouse preimplantation embryos. In this study, we found H3K27me3 is strongly biased towar...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.323105.118
更新日期:2019-04-01 00:00:00
abstract::We report a systematic mutational analysis of the helix-turn-helix motif (HTH) of the fushi tarazu (ftz) homeo domain (HD) of Drosophila. We started out by testing the function of chimeric ftz proteins containing either a part of the Sex combs reduced (Scr) or the muscle segment homeobox (msh) HDs. By complementation ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.1082
更新日期:1992-06-01 00:00:00