TRAF2 phosphorylation modulates tumor necrosis factor alpha-induced gene expression and cell resistance to apoptosis.


:TRAF2 is an adaptor protein that regulates the activation of the c-Jun N-terminal kinase (JNK) and IkappaB kinase (IKK) signaling cascades in response to tumor necrosis factor alpha (TNF-alpha) stimulation. Although the downstream events in TNF-alpha signaling are better understood, the membrane-proximal events are still elusive. Here, we demonstrate that TNF-alpha and cellular stresses induce TRAF2 phosphorylation at serine 11 and that this phosphorylation is required for the expression of a subset of NF-kappaB target genes. Although TRAF2 phosphorylation had a minimal effect on the TNF-alpha-induced rapid and transient IKK activation, it was essential for secondary and prolonged IKK activation. Consistent with this, TRAF2 phosphorylation is not required for its recruitment to the TNFR1 complex in response to TNF-alpha stimulation but is required for its association with a cytoplasmic complex containing RIP1 and IKK. In addition, TRAF2 phosphorylation was essential for the full TNF-alpha-induced activation of JNK. Notably, TRAF2 phosphorylation increased both basal and inducible c-Jun and NF-kappaB activities and rendered cells resistant to stress-induced apoptosis. Moreover, TRAF2 was found to be constitutively phosphorylated in some lymphomas. These results unveil a new, finely tuned mechanism for TNF-alpha-induced IKK activation modulated by TRAF2 phosphorylation and suggest that TRAF2 phosphorylation contributes to elevated levels of basal NF-kappaB activity in certain human cancers.


Mol Cell Biol


Blackwell K,Zhang L,Thomas GS,Sun S,Nakano H,Habelhah H




Has Abstract


2009-01-01 00:00:00














  • Deletions of N-terminal sequences of polyoma virus T-antigens reduce but do not abolish transformation of rat fibroblasts.

    abstract::Polyoma virus transforms, upon infection or DNA transfection, nonpermissive Fisher rat fibroblasts. Cloned viral DNA was deleted of sequences around the Bg/I site at nucleotide 86 by Bal31 nuclease treatment and then recloned in Escherichia coli. The extent of deletion for each mutant was then determined by DNA sequen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Katinka M,Yaniv M

    更新日期:1982-10-01 00:00:00

  • Induction of yeast histone genes by stimulation of stationary-phase cells.

    abstract::In the cell cycle of the budding yeast Saccharomyces cerevisiae, expression of the histone genes H2A and H2B of the TRT1 and TRT2 loci is regulated by the performance of "start," the step that also regulates the cell cycle. Here we show that histone production is also subject to an additional form of regulation that i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Drebot MA,Veinot-Drebot LM,Singer RA,Johnston GC

    更新日期:1990-12-01 00:00:00

  • AFR1 promotes polarized apical morphogenesis in Saccharomyces cerevisiae.

    abstract::The G protein-coupled alpha-factor receptor promotes polarized growth toward a mating partner. alpha-Factor induces the expression of AFR1, which acts together with the receptor C terminus to promote normal morphogenesis. The function of AFR1 was investigated by engineering cells to constitutively express AFR1 without...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Konopka JB,DeMattei C,Davis C

    更新日期:1995-02-01 00:00:00

  • Diacylglycerol production in Xenopus laevis oocytes after microinjection of p21ras proteins is a consequence of activation of phosphatidylcholine metabolism.

    abstract::Microinjection of p21Ha-ras proteins into Xenopus laevis oocytes induces a rapid increase of 1,2-diacylglycerol (DAG) levels. The observed alterations in DAG levels were consistent with the ability of the protein to induce maturation, measured by germinal vesicle breakdown (GVBD). Both the increase in DAG levels and G...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lacal JC

    更新日期:1990-01-01 00:00:00

  • Dominant active alleles of RIM101 (PRR2) bypass the pH restriction on filamentation of Candida albicans.

    abstract::Morphological development of the fungal pathogen Candida albicans is profoundly affected by ambient pH. Acidic pH restricts growth to the yeast form, whereas neutral pH permits development of the filamentous form. Superimposed on the pH restriction is a temperature requirement of approximately 37 degrees C for filamen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: El Barkani A,Kurzai O,Fonzi WA,Ramon A,Porta A,Frosch M,Mühlschlegel FA

    更新日期:2000-07-01 00:00:00

  • The cellular response to neuregulins is governed by complex interactions of the erbB receptor family.

    abstract::Deregulated signaling by the four members of the epidermal growth factor receptor tyrosine kinase family (erbB family) is implicated in the genesis or progression of human cancers. However, efforts to analyze signaling by these receptors have been hampered by the diversity of ligands and extensive interreceptor cross ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Riese DJ 2nd,van Raaij TM,Plowman GD,Andrews GC,Stern DF

    更新日期:1995-10-01 00:00:00

  • Wing-to-Leg homeosis by spineless causes apoptosis regulated by Fish-lips, a novel leucine-rich repeat transmembrane protein.

    abstract::Growth, patterning, and apoptosis are mutually interactive during development. For example, cells that select an abnormal fate in a developing field are frequently removed by apoptosis. An important issue in this process that needs to be resolved is the mechanism used by cells to discern their correct fate from an abn...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Adachi-Yamada T,Harumoto T,Sakurai K,Ueda R,Saigo K,O'Connor MB,Nakato H

    更新日期:2005-04-01 00:00:00

  • Induction of RNA editing at heterologous sites by sequences in apolipoprotein B mRNA.

    abstract::An RNA editing mechanism modifies apolipoprotein B (apo-B) mRNA in the intestine by converting cytosine at nucleotide (nt) 6666 to uracil. To define the sequence requirements for editing, mutant apo-B RNAs were analyzed for the ability to be edited in vitro by enterocyte extracts. Editing was detected by a sensitive a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Driscoll DM,Lakhe-Reddy S,Oleksa LM,Martinez D

    更新日期:1993-12-01 00:00:00

  • Methylation and rearrangement of mouse intracisternal a particle genes in development, aging, and myeloma.

    abstract::Sequences of DNA that hybridize on Southern blots with cloned intracisternal A-particle (IAP) sequences have been examined in genomic DNAs of neonatal mice, livers of adult mice (3, 6, 12, 18, 24, and 26 months old), and the solid myeloma tumor MOPC-315. The isoschizomers HpaII (CCGG or mCCGG) and MspI (CCGG or CmCGG)...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Mays-Hoopes LL,Brown A,Huang RC

    更新日期:1983-08-01 00:00:00

  • ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites.

    abstract::The Eph receptors are the largest known family of receptor tyrosine kinases and are notable for distinctive expression patterns in the nervous system and in early vertebrate development. However, all were identified as orphan receptors, and only recently have there been descriptions of a corresponding family of ligand...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Bergemann AD,Cheng HJ,Brambilla R,Klein R,Flanagan JG

    更新日期:1995-09-01 00:00:00

  • Analysis of Small Critical Regions of Swi1 Conferring Prion Formation, Maintenance, and Transmission.

    abstract::Saccharomyces cerevisiae contains several prion elements, which are epigenetically transmitted as self-perpetuating protein conformations. One such prion is [SWI + ], whose protein determinant is Swi1, a subunit of the SWI/SNF chromatin-remodeling complex. We previously rep...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Valtierra S,Du Z,Li L

    更新日期:2017-09-26 00:00:00

  • Canonical Notch signaling is dispensable for early cell fate specifications in mammals.

    abstract::The canonical Notch signaling pathway mediated by Delta- and Jagged-like Notch ligands determines a variety of cell fates in metazoa. In Caenorhabditis elegans and sea urchins, canonical Notch signaling is essential for different cell fate specifications during early embryogenesis or the formation of endoderm, mesoder...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Shi S,Stahl M,Lu L,Stanley P

    更新日期:2005-11-01 00:00:00

  • Caspase activity is required for engulfment of apoptotic cells.

    abstract::Clearance of apoptotic cells by phagocytic neighbors is crucial for normal development of multicellular organisms. However, how phagocytes discriminate between healthy and dying cells remains poorly understood. We focus on glial phagocytosis of apoptotic neurons during development of the Drosophila central nervous sys...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Shklyar B,Levy-Adam F,Mishnaevski K,Kurant E

    更新日期:2013-08-01 00:00:00

  • Human MDM2 isoforms translated differentially on constitutive versus p53-regulated transcripts have distinct functions in the p53/MDM2 and TSG101/MDM2 feedback control loops.

    abstract::Proteins encoded by the mdm2 gene, which has a pivotal role in the regulation of growth and differentiation, exist principally in human and murine cells as two isoforms that migrate in gels as 75-kDa and 90-kDa proteins. There is limited understanding of the respective biological roles of these isoforms, their molecul...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Cheng TH,Cohen SN

    更新日期:2007-01-01 00:00:00

  • Cyclophilin A peptidyl-prolyl isomerase activity promotes ZPR1 nuclear export.

    abstract::The peptidyl-prolyl isomerase (PPIase) cyclophilin A (Cpr1p) is conserved from eubacteria to mammals, yet its biological function has resisted elucidation. Unable to identify a phenotype that is suggestive of Cpr1p's function in a cpr1Delta Saccharomyces cerevisiae strain, we screened for CPR1-dependent strains. In al...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ansari H,Greco G,Luban J

    更新日期:2002-10-01 00:00:00

  • Ionophore-resistant mutants of Toxoplasma gondii reveal host cell permeabilization as an early event in egress.

    abstract::Toxoplasma gondii is an obligate intracellular pathogen within the phylum Apicomplexa. Invasion and egress by this protozoan parasite are rapid events that are dependent upon parasite motility and appear to be directed by fluctuations in intracellular [Ca(2+)]. Treatment of infected host cells with the calcium ionopho...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Black MW,Arrizabalaga G,Boothroyd JC

    更新日期:2000-12-01 00:00:00

  • Ribosomal protein S25 dependency reveals a common mechanism for diverse internal ribosome entry sites and ribosome shunting.

    abstract::During viral infection or cellular stress, cap-dependent translation is shut down. Proteins that are synthesized under these conditions use alternative mechanisms to initiate translation. This study demonstrates that at least two alternative translation initiation routes, internal ribosome entry site (IRES) initiation...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hertz MI,Landry DM,Willis AE,Luo G,Thompson SR

    更新日期:2013-03-01 00:00:00

  • Interactions of the Mcm1 MADS box protein with cofactors that regulate mating in yeast.

    abstract::The yeast Mcm1 protein is a member of the MADS box family of transcriptional regulatory factors, a class of DNA-binding proteins that control numerous cellular and developmental processes in yeast, Drosophila melanogaster, plants, and mammals. Although these proteins bind DNA on their own, they often combine with diff...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Mead J,Bruning AR,Gill MK,Steiner AM,Acton TB,Vershon AK

    更新日期:2002-07-01 00:00:00

  • Extrachromosomal replication of shuttle vectors in Dictyostelium discoideum.

    abstract::We cloned a 12.3-kilobase (kb) endogenous plasmid, Ddp1, found in several wild-type and laboratory strains of Dictyostelium discoideum into pBR322. The cloned plasmids have been used to cotransform D. discoideum cells with B10S, a transformation vector carrying a gene fusion conferring resistance to G418. Whereas B10S...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Firtel RA,Silan C,Ward TE,Howard P,Metz BA,Nellen W,Jacobson A

    更新日期:1985-11-01 00:00:00

  • Role for Nhp6, Gcn5, and the Swi/Snf complex in stimulating formation of the TATA-binding protein-TFIIA-DNA complex.

    abstract::The TATA-binding protein (TBP), TFIIA, and TFIIB interact with promoter DNA to form a complex required for transcriptional initiation, and many transcriptional regulators function by either stimulating or inhibiting formation of this complex. We have recently identified TBP mutants that are viable in wild-type cells b...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Biswas D,Imbalzano AN,Eriksson P,Yu Y,Stillman DJ

    更新日期:2004-09-01 00:00:00

  • Insulin stimulates syntaxin4 SNARE complex assembly via a novel regulatory mechanism.

    abstract::Insulin stimulates glucose transport into fat and muscle cells by increasing the exocytic trafficking rate of the GLUT4 facilitative glucose transporter from intracellular stores to the plasma membrane. Delivery of GLUT4 to the plasma membrane is mediated by formation of functional SNARE complexes containing syntaxin4...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kioumourtzoglou D,Gould GW,Bryant NJ

    更新日期:2014-04-01 00:00:00

  • Matrix attachment regions are positioned near replication initiation sites, genes, and an interamplicon junction in the amplified dihydrofolate reductase domain of Chinese hamster ovary cells.

    abstract::Genomic DNA in higher eucaryotic cells is organized into a series of loops, each of which may be affixed at its base to the nuclear matrix via a specific matrix attachment region (MAR). In this report, we describe the distribution of MARs within the amplified dihydrofolate reductase (DHFR) domain (amplicon) in the met...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Dijkwel PA,Hamlin JL

    更新日期:1988-12-01 00:00:00

  • O-GlcNAcylation Signal Mediates Proteasome Inhibitor Resistance in Cancer Cells by Stabilizing NRF1.

    abstract::Cancer cells often heavily depend on the ubiquitin-proteasome system (UPS) for their growth and survival. Irrespective of their strong dependence on the proteasome activity, cancer cells, except for multiple myeloma, are mostly resistant to proteasome inhibitors. A major cause of this resistance is the proteasome boun...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sekine H,Okazaki K,Kato K,Alam MM,Shima H,Katsuoka F,Tsujita T,Suzuki N,Kobayashi A,Igarashi K,Yamamoto M,Motohashi H

    更新日期:2018-08-15 00:00:00

  • Activation of EphA receptors mediates the recruitment of the adaptor protein Slap, contributing to the downregulation of N-methyl-D-aspartate receptors.

    abstract::Regulation of the activity of N-methyl-d-aspartate receptors (NMDARs) at glutamatergic synapses is essential for certain forms of synaptic plasticity underlying learning and memory and is also associated with neurotoxicity and neurodegenerative diseases. In this report, we investigate the role of Src-like adaptor prot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Semerdjieva S,Abdul-Razak HH,Salim SS,Yáñez-Muñoz RJ,Chen PE,Tarabykin V,Alifragis P

    更新日期:2013-04-01 00:00:00

  • A vascular gene trap screen defines RasGRP3 as an angiogenesis-regulated gene required for the endothelial response to phorbol esters.

    abstract::We identified Ras guanine-releasing protein 3 (RasGRP3) as a guanine exchange factor expressed in blood vessels via an embryonic stem (ES) cell-based gene trap screen to identify novel vascular genes. RasGRP3 is expressed in embryonic blood vessels, down-regulated in mature adult vessels, and reexpressed in newly form...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Roberts DM,Anderson AL,Hidaka M,Swetenburg RL,Patterson C,Stanford WL,Bautch VL

    更新日期:2004-12-01 00:00:00

  • Developmental regulation of human gamma-globin genes in transgenic mice.

    abstract::We report results showing that several gamma gene promoter elements participate in the developmental control of gamma-globin genes. Four gamma gene constructs with 5' truncated at -141, -201, -382, and -730 of the A gamma gene promoter linked to a micro locus control region (microLCR) cassette were used for production...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Stamatoyannopoulos G,Josephson B,Zhang JW,Li Q

    更新日期:1993-12-01 00:00:00

  • TAF1 histone acetyltransferase activity in Sp1 activation of the cyclin D1 promoter.

    abstract::A missense mutation within the histone acetyltransferase (HAT) domain of the TATA binding protein-associated factor TAF1 induces ts13 cells to undergo a late G(1) arrest and decreases cyclin D1 transcription. We have found that TAF1 mutants (Delta844-850 and Delta848-850, from which amino acids 844 through 850 and 848...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hilton TL,Li Y,Dunphy EL,Wang EH

    更新日期:2005-05-01 00:00:00

  • DNA elements regulating alpha1-tubulin gene induction during regeneration of eukaryotic flagella.

    abstract::Eukaryotic flagella are complex organelles composed of more than 200 polypeptides. Little is known about the regulatory mechanisms governing synthesis of the flagellar protein subunits and their assembly into this complex organelle. The unicellular green alga Chlamydomonas reinhardtii is the premier experimental model...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Periz G,Keller LR

    更新日期:1997-07-01 00:00:00

  • Growth Factor Independence 1B-Mediated Transcriptional Repression and Lineage Allocation Require Lysine-Specific Demethylase 1-Dependent Recruitment of the BHC Complex.

    abstract::Growth factor independence 1B (GFI1B) coordinates assembly of transcriptional repressor complexes comprised of corepressors and histone-modifying enzymes to control gene expression programs governing lineage allocation in hematopoiesis. Enforced expression of GFI1B in K562 erythroleukemia cells favors erythroid over m...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: McClellan D,Casey MJ,Bareyan D,Lucente H,Ours C,Velinder M,Singer J,Lone MD,Sun W,Coria Y,Mason CC,Engel ME

    更新日期:2019-06-13 00:00:00

  • ADA5/SPT20 links the ADA and SPT genes, which are involved in yeast transcription.

    abstract::In this report we described the cloning and characterization of ADA5, a gene identified by resistance to GAL4-VP16-mediated toxicity. ADA5 binds directly to the VP16 activation domain but not to a transcriptionally defective VP16 double point mutant. Double mutants with mutations in ada5 and other genes (ada2 or ada3)...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Marcus GA,Horiuchi J,Silverman N,Guarente L

    更新日期:1996-06-01 00:00:00