Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor.

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 Dev

journal_title

Genes & development

authors

Niu H,Ye BH,Dalla-Favera R

doi

10.1101/gad.12.13.1953

subject

Has Abstract

pub_date

1998-07-01 00:00:00

pages

1953-61

issue

13

eissn

0890-9369

issn

1549-5477

journal_volume

12

pub_type

杂志文章
  • Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1.

    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

    authors: Bhattacharya S,Michels CL,Leung MK,Arany ZP,Kung AL,Livingston DM

    更新日期:1999-01-01 00:00:00

  • Transcriptional activity of pannier is regulated negatively by heterodimerization of the GATA DNA-binding domain with a cofactor encoded by the u-shaped gene of Drosophila.

    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

    authors: Haenlin M,Cubadda Y,Blondeau F,Heitzler P,Lutz Y,Simpson P,Ramain P

    更新日期:1997-11-15 00:00:00

  • MVH in piRNA processing and gene silencing of retrotransposons.

    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

    authors: Kuramochi-Miyagawa S,Watanabe T,Gotoh K,Takamatsu K,Chuma S,Kojima-Kita K,Shiromoto Y,Asada N,Toyoda A,Fujiyama A,Totoki Y,Shibata T,Kimura T,Nakatsuji N,Noce T,Sasaki H,Nakano T

    更新日期:2010-05-01 00:00:00

  • USP21 deubiquitinase promotes pancreas cancer cell stemness via Wnt pathway activation.

    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

    authors: Hou P,Ma X,Zhang Q,Wu CJ,Liao W,Li J,Wang H,Zhao J,Zhou X,Guan C,Ackroyd J,Jiang S,Zhang J,Spring DJ,Wang YA,DePinho RA

    更新日期:2019-10-01 00:00:00

  • Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development.

    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

    authors: Michaelson JS,Bader D,Kuo F,Kozak C,Leder P

    更新日期:1999-08-01 00:00:00

  • Control of translation and mRNA degradation by miRNAs and siRNAs.

    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

    authors: Valencia-Sanchez MA,Liu J,Hannon GJ,Parker R

    更新日期:2006-03-01 00:00:00

  • Suppression of a cold-sensitive mutation in 16S rRNA by overexpression of a novel ribosome-binding factor, RbfA.

    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

    authors: Dammel CS,Noller HF

    更新日期:1995-03-01 00:00:00

  • JAK2 is dispensable for maintenance of JAK2 mutant B-cell acute lymphoblastic leukemias.

    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

    authors: Kim SK,Knight DA,Jones LR,Vervoort S,Ng AP,Seymour JF,Bradner JE,Waibel M,Kats L,Johnstone RW

    更新日期:2018-06-01 00:00:00

  • A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export.

    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

    authors: Lee MS,Henry M,Silver PA

    更新日期:1996-05-15 00:00:00

  • Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B.

    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

    authors: Kao CF,Hillyer C,Tsukuda T,Henry K,Berger S,Osley MA

    更新日期:2004-01-15 00:00:00

  • Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing, and alternative polyA site selection.

    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

    authors: Avendaño-Vázquez SE,Dhir A,Bembich S,Buratti E,Proudfoot N,Baralle FE

    更新日期:2012-08-01 00:00:00

  • The stringent response in Myxococcus xanthus is regulated by SocE and the CsgA C-signaling protein.

    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:

    authors: Crawford EW Jr,Shimkets LJ

    更新日期:2000-02-15 00:00:00

  • CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons.

    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

    authors: Oury F,Yadav VK,Wang Y,Zhou B,Liu XS,Guo XE,Tecott LH,Schutz G,Means AR,Karsenty G

    更新日期:2010-10-15 00:00:00

  • Suppressors of a U4 snRNA mutation define a novel U6 snRNP protein with RNA-binding motifs.

    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

    authors: Shannon KW,Guthrie C

    更新日期:1991-05-01 00:00:00

  • Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function.

    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

    authors: Bugge A,Feng D,Everett LJ,Briggs ER,Mullican SE,Wang F,Jager J,Lazar MA

    更新日期:2012-04-01 00:00:00

  • Mechanism of corepressor binding and release from nuclear hormone receptors.

    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

    authors: Nagy L,Kao HY,Love JD,Li C,Banayo E,Gooch JT,Krishna V,Chatterjee K,Evans RM,Schwabe JW

    更新日期:1999-12-15 00:00:00

  • Wild-type and cancer-related p53 proteins are preferentially degraded by MDM2 as dimers rather than tetramers.

    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

    authors: Katz C,Low-Calle AM,Choe JH,Laptenko O,Tong D,Joseph-Chowdhury JN,Garofalo F,Zhu Y,Friedler A,Prives C

    更新日期:2018-03-01 00:00:00

  • p53 is essential for DNA methylation homeostasis in naïve embryonic stem cells, and its loss promotes clonal heterogeneity.

    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

    authors: Tovy A,Spiro A,McCarthy R,Shipony Z,Aylon Y,Allton K,Ainbinder E,Furth N,Tanay A,Barton M,Oren M

    更新日期:2017-05-15 00:00:00

  • Ste20-like protein kinases are required for normal localization of cell growth and for cytokinesis in budding yeast.

    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

    authors: Cvrcková F,De Virgilio C,Manser E,Pringle JR,Nasmyth K

    更新日期:1995-08-01 00:00:00

  • Stepwise and dynamic assembly of the earliest precursors of small ribosomal subunits in yeast.

    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

    authors: Zhang L,Wu C,Cai G,Chen S,Ye K

    更新日期:2016-03-15 00:00:00

  • Nuclear polyadenylation factors recognize cytoplasmic polyadenylation elements.

    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

    authors: Bilger A,Fox CA,Wahle E,Wickens M

    更新日期:1994-05-01 00:00:00

  • The p110α and p110β isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis.

    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

    authors: Utermark T,Rao T,Cheng H,Wang Q,Lee SH,Wang ZC,Iglehart JD,Roberts TM,Muller WJ,Zhao JJ

    更新日期:2012-07-15 00:00:00

  • Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination.

    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

    authors: Carmona LM,Fugmann SD,Schatz DG

    更新日期:2016-04-15 00:00:00

  • Bacterial promoter architecture: subsite structure of UP elements and interactions with the carboxy-terminal domain of the RNA polymerase alpha subunit.

    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

    authors: Estrem ST,Ross W,Gaal T,Chen ZW,Niu W,Ebright RH,Gourse RL

    更新日期:1999-08-15 00:00:00

  • A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice.

    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

    authors: Frescas D,de Lange T

    更新日期:2014-01-15 00:00:00

  • Selection of the initiator tRNA by Escherichia coli initiation factors.

    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

    authors: Hartz D,McPheeters DS,Gold L

    更新日期:1989-12-01 00:00:00

  • Reconstitution of human TFIIA activity from recombinant polypeptides: a role in TFIID-mediated transcription.

    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

    authors: Sun X,Ma D,Sheldon M,Yeung K,Reinberg D

    更新日期:1994-10-01 00:00:00

  • Mechanistic insights and identification of two novel factors in the C. elegans NMD pathway.

    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

    authors: Longman D,Plasterk RH,Johnstone IL,Cáceres JF

    更新日期:2007-05-01 00:00:00

  • Molecular mechanisms of Spemann's organizer formation: conserved growth factor synergy between Xenopus and mouse.

    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

    authors: Watabe T,Kim S,Candia A,Rothbächer U,Hashimoto C,Inoue K,Cho KW

    更新日期:1995-12-15 00:00:00

  • A yeast protein that influences the chromatin structure of UASG and functions as a powerful auxiliary gene activator.

    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

    authors: Chasman DI,Lue NF,Buchman AR,LaPointe JW,Lorch Y,Kornberg RD

    更新日期:1990-04-01 00:00:00