Abstract:
:The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor expressed in germinal center (GC) B and T cells and required for GC formation and antibody affinity maturation. Deregulation of bcl-6 expression by chromosomal rearrangements and point mutations of the bcl-6 promoter region are implicated in the pathogenesis of B-cell lymphoma. The signals regulating bcl-6 expression are not known. Here we show that antigen receptor activation leads to BCL-6 phosphorylation by mitogen-activated protein kinase (MAPK). Phosphorylation, in turn, targets BCL-6 for rapid degradation by the ubiquitin/proteasome pathway. These findings indicate that BCL-6 expression is directly controlled by the antigen receptor via MAPK activation. This signaling pathway may be crucial for the control of B-cell differentiation and antibody response and has implications for the regulation of other POZ/zinc finger transcription factors in other tissues.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Niu H,Ye BH,Dalla-Favera Rdoi
10.1101/gad.12.13.1953subject
Has Abstractpub_date
1998-07-01 00:00:00pages
1953-61issue
13eissn
0890-9369issn
1549-5477journal_volume
12pub_type
杂志文章abstract::Recruitment of p300/CBP by the hypoxia-inducible factor, HIF-1, is essential for the transcriptional response to hypoxia and requires an interaction between the p300/CBP CH1 region and HIF-1alpha. A new p300-CH1 interacting protein, p35srj, has been identified and cloned. p35srj is an alternatively spliced isoform of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.1.64
更新日期:1999-01-01 00:00:00
abstract::The genes pannier (pnr) and u-shaped (ush) are required for the regulation of achaete-scute during establishment of the bristle pattern in Drosophila. pnr encodes a protein belonging to the GATA family of transcription factors, whereas ush encodes a novel zinc finger protein. Genetic interactions between dominant pnr ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.22.3096
更新日期:1997-11-15 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::The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates m...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.326314.119
更新日期:2019-10-01 00:00:00
abstract::The mammalian Daxx gene has been identified in a diverse set of yeast interaction trap experiments. Although a facilitating role for Daxx in Fas-induced apoptosis has been suggested, Daxx's physiologic function remains unknown. To elucidate the in vivo role of Daxx, we have generated Daxx-deficient mice. Surprisingly,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.15.1918
更新日期:1999-08-01 00:00:00
abstract::The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1399806
更新日期:2006-03-01 00:00:00
abstract::A novel 15-kDa protein, RbfA, has been identified by virtue of its ability to act as a high copy suppressor of a previously characterized dominant cold-sensitive mutation (C23U) in 16S rRNA. RbfA is found associated with free 30S ribosomal subunits, but not with 70S ribosomes or polysomes, and is essential for maximal...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.5.626
更新日期:1995-03-01 00:00:00
abstract::Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cell acute lymphoblastic leukemia (B-ALL). In preclinical studies, treatment of JAK2 mutant leukemias with type I JAK2 inhibitors (e.g., Food and Drug Administration [FDA]-approved ruxolitinib...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.307504.117
更新日期:2018-06-01 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::Covalent modifications of the histone N tails play important roles in eukaryotic gene expression. Histone acetylation, in particular, is required for the activation of a subset of eukaryotic genes through the targeted recruitment of histone acetyltransferases. We have reported that a histone C tail modification, ubiqu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1149604
更新日期:2004-01-15 00:00:00
abstract::TDP-43 is a critical RNA-binding factor associated with pre-mRNA splicing in mammals. Its expression is tightly autoregulated, with loss of this regulation implicated in human neuropathology. We demonstrate that TDP-43 overexpression in humans and mice activates a 3' untranslated region (UTR) intron, resulting in exci...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.194829.112
更新日期:2012-08-01 00:00:00
abstract::Myxococcus xanthus fruiting body development is induced by amino acid limitation. The decision to grow or develop is established by the RelA-dependent stringent response and A-signaling. We identified two new members of this regulatory hierarchy, socE and the C-signaling gene csgA. SocE depletion arrests growth and in...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-02-15 00:00:00
abstract::Serotonin is a bioamine regulating bone mass accrual differently depending on its site of synthesis. It decreases accrual when synthesized in the gut, and increases it when synthesized in the brain. The signal transduction events elicited by gut-derived serotonin once it binds to the Htr1b receptor present on osteobla...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1977210
更新日期:2010-10-15 00:00:00
abstract::U4 and U6 small nuclear RNAs are associated by an extensive base-pairing interaction that must be disrupted and reformed with each round of splicing. U4 mutations within the U4/U6 interaction domain destabilize the complex in vitro and cause a cold-sensitive phenotype in vivo. Restabilization of the U4/U6 helix by dom...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.5.773
更新日期:1991-05-01 00:00:00
abstract::The nuclear receptor Rev-erbα regulates circadian rhythm and metabolism, but its effects are modest and it has been considered to be a secondary regulator of the cell-autonomous clock. Here we report that depletion of Rev-erbα together with closely related Rev-erbβ has dramatic effects on the cell-autonomous clock as ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.186858.112
更新日期:2012-04-01 00:00:00
abstract::The association of transcription corepressors SMRT and N-CoR with retinoid and thyroid receptors results in suppression of basal transcriptional activity. A key event in nuclear receptor signaling is the hormone-dependent release of corepressor and the recruitment of coactivator. Biochemical and structural studies hav...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.24.3209
更新日期:1999-12-15 00:00:00
abstract::The p53 tumor suppressor protein is the most well studied as a regulator of transcription in the nucleus, where it exists primarily as a tetramer. However, there are other oligomeric states of p53 that are relevant to its regulation and activities. In unstressed cells, p53 is normally held in check by MDM2 that target...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.304071.117
更新日期:2018-03-01 00:00:00
abstract::DNA methylation is a key regulator of embryonic stem cell (ESC) biology, dynamically changing between naïve, primed, and differentiated states. The p53 tumor suppressor is a pivotal guardian of genomic stability, but its contributions to epigenetic regulation and stem cell biology are less explored. We report that, in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.299198.117
更新日期:2017-05-15 00:00:00
abstract::The yeast Ste20 protein kinase is involved in pheromone response. Mammalian homologs of Ste20 exist, but their function remains unknown. We identified a novel yeast STE20 homolog, CLA4, in a screen for mutations lethal in the absence of the G1 cyclins Cln1 and Cln2. Cla4 is involved in budding and cytokinesis and inte...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.15.1817
更新日期:1995-08-01 00:00:00
abstract::The eukaryotic ribosomal RNA (rRNA) is associated cotranscriptionally with numerous factors into an enormous 90S preribosomal particle that conducts early processing of small ribosomal subunits. The assembly pathway and structure of the 90S particle is poorly understood. Here, we affinity-purified and analyzed the con...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.274688.115
更新日期:2016-03-15 00:00:00
abstract::In the cytoplasm of oocytes and early embryos, addition of poly(A) to mRNAs can activate their translation. We demonstrate that despite many differences between poly(A) addition in the cytoplasm and nucleus, these two forms of polyadenylation may involve identical trans-acting factors. Nuclear polyadenylation requires...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.9.1106
更新日期:1994-05-01 00:00:00
abstract::Class Ia phosphatidylinositol 3 kinase (PI3K) is required for oncogenic receptor-mediated transformation; however, the individual roles of the two commonly expressed class Ia PI3K isoforms in oncogenic receptor signaling have not been elucidated in vivo. Here, we show that genetic ablation of p110α blocks tumor format...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.191973.112
更新日期:2012-07-15 00:00:00
abstract::The recombination-activating gene 1 (RAG1) and RAG2 proteins initiate V(D)J recombination, the process that assembles the B- and T-lymphocyte antigen receptor genes of jawed vertebrates. RAG1 and RAG2 are thought to have arisen from a transposable element, but the origins of this element are not understood. We show th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.278432.116
更新日期:2016-04-15 00:00:00
abstract::We demonstrate here that the previously described bacterial promoter upstream element (UP element) consists of two distinct subsites, each of which, by itself, can bind the RNA polymerase holoenzyme alpha subunit carboxy-terminal domain (RNAP alphaCTD) and stimulate transcription. Using binding-site-selection experime...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.16.2134
更新日期:1999-08-15 00:00:00
abstract::The progressive bone marrow failure syndrome dyskeratosis congenita (DC) is often caused by mutations in telomerase or the factors involved in telomerase biogenesis and trafficking. However, a subset of DC patients is heterozygous for mutations in the shelterin component TIN2. To determine how the TIN2-DC mutations af...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.233395.113
更新日期:2014-01-15 00:00:00
abstract::We have developed a new technique, called 'toeprinting,' which has allowed a study of the tRNA-binding properties of Escherichia coli translation initiation complexes. In response to natural mRNAs, the initiator tRNA and a variety of elongator tRNAs bind to the same tRNA-binding site on the 30S ribosomal subunit as lo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.12a.1899
更新日期:1989-12-01 00:00:00
abstract::Human TFIIA activity is composed of three subunits (alpha, beta, gamma). Here we report the isolation of a human cDNA clone encoding the gamma-subunit and the reconstitution of TFIIA activity from recombinant polypeptides (holo-TFIIA). Protein-protein interaction analysis established that the beta and gamma subunits o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.19.2336
更新日期:1994-10-01 00:00:00
abstract::The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417707
更新日期:2007-05-01 00:00:00
abstract::Mesoderm induction assays in Xenopus have implicated growth factors such as activin, Vg1, Xwnt-8, and noggin as important in directing the formation of dorsal mesoderm (Spemann's organizer). Because these growth factors are structurally very different, they presumably act through distinct cell surface receptors that i...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.24.3038
更新日期:1995-12-15 00:00:00
abstract::GRF2, an abundant yeast protein of Mr approximately 127,000, binds to the GAL upstream activating sequence (UASG) and creates a nucleosome-free region of approximately 230 bp. Purified GRF2 binds to sequences found in many other UASs, in the 35S rRNA enhancer, at centromeres, and at telomeres. Although GRF2 stimulates...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.503
更新日期:1990-04-01 00:00:00