Myc family oncoproteins function through a common pathway to transform normal cells in culture: cross-interference by Max and trans-acting dominant mutants.


:The myc family of cellular oncogenes encodes three highly related nuclear phosphoproteins (c-Myc, N-Myc, and L-Myc) that are believed to function as sequence-specific transcription factors capable of regulating genes important in cellular growth and differentiation. Current evidence indicates that Myc family proteins exist as biologically active heterodimeric complexes in association with another helix-loop-helix leucine zipper phosphoprotein, Max. We have investigated the common and unique properties among the Myc family, as well as the physiological role of Max in the regulation of Myc family function. We demonstrate that trans-activation-incompetent mutants of one Myc family member can act in trans to dominantly suppress the cotransformation activities of all three Myc oncoproteins, indicating that the Myc family functions through common genetic elements in its cellular transformation pathways. Employing co-immunoprecipitation with either anti-Myc or anti-Max antibodies, we show that the transfected normal c-Myc, N-Myc, and L-Myc oncoproteins associate with the endogenous Max protein in REF transformants, indicating that the Max interaction represents at least one component common to Myc family function. In addition, we observed a striking reduction in Myc cotransformation activity when a Max expression construct was added to myc/ras co-transfections. We discuss these biological findings in the context of a proposed model for Myc/Max function and regulation in which Max serves as either an obligate partner in the Myc/Max transcriptional complex or as a repressor in the form of a transcriptionally inert Max/Max homodimer capable of occupying Myc/Max-responsive gene targets.


Genes Dev


Genes & development


Mukherjee B,Morgenbesser SD,DePinho RA




Has Abstract


1992-08-01 00:00:00












  • Ferredoxin reductase is critical for p53-dependent tumor suppression via iron regulatory protein 2.

    abstract::Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Zhang Y,Qian Y,Zhang J,Yan W,Jung YS,Chen M,Huang E,Lloyd K,Duan Y,Wang J,Liu G,Chen X

    更新日期:2017-06-15 00:00:00

  • Incomplete replication generates somatic DNA alterations within Drosophila polytene salivary gland cells.

    abstract::DNA replication remains unfinished in many Drosophila polyploid cells, which harbor disproportionately fewer copies of late-replicating chromosomal regions. By analyzing paired-end high-throughput sequence data from polytene larval salivary gland cells, we define 112 underreplicated (UR) euchromatic regions 60-480 kb ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Yarosh W,Spradling AC

    更新日期:2014-08-15 00:00:00

  • Identification of cis-acting sites for condensin loading onto budding yeast chromosomes.

    abstract::Eukaryotic chromosomes reach their stable rod-shaped appearance in mitosis in a reaction dependent on the evolutionarily conserved condensin complex. Little is known about how and where condensin associates with chromosomes. Here, we analyze condensin binding to budding yeast chromosomes using high-resolution oligonuc...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: D'Ambrosio C,Schmidt CK,Katou Y,Kelly G,Itoh T,Shirahige K,Uhlmann F

    更新日期:2008-08-15 00:00:00

  • Calcineurin-dependent regulation of Crz1p nuclear export requires Msn5p and a conserved calcineurin docking site.

    abstract::Calcineurin, a conserved Ca(2+)/calmodulin-regulated protein phosphatase, plays a crucial role in Ca(2+) signaling in a wide variety of cell types. In Saccharomyces cerevisiae, calcineurin positively regulates transcription in response to stress by dephosphorylating the transcription factor Crz1p/Tcn1p. Dephosphorylat...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Boustany LM,Cyert MS

    更新日期:2002-03-01 00:00:00

  • Evidence for a novel protease governing regulated intramembrane proteolysis and resistance to antimicrobial peptides in Bacillus subtilis.

    abstract::Evidence is presented that the activation of the RNA polymerase sigma factor sigma(W) in Bacillus subtilis by regulated intramembrane proteolysis is governed by a novel, membrane-embedded protease. The sigma(W) factor is activated by proteolytic destruction of the membrane-bound anti-sigma(W) factor RsiW in response t...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Ellermeier CD,Losick R

    更新日期:2006-07-15 00:00:00

  • Constitutive mTORC1 activation by a herpesvirus Akt surrogate stimulates mRNA translation and viral replication.

    abstract::All viruses require cellular ribosomes to translate their mRNAs. Viruses producing methyl-7 (m⁷) GTP-capped mRNAs, like Herpes Simplex Virus-1 (HSV-1), stimulate cap-dependent translation by activating mTORC1 to inhibit the translational repressor 4E-binding protein 1 (4E-BP1). Here, we establish that the HSV-1 kinase...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Chuluunbaatar U,Roller R,Feldman ME,Brown S,Shokat KM,Mohr I

    更新日期:2010-12-01 00:00:00

  • Inflammation and Hras signaling control epithelial-mesenchymal transition during skin tumor progression.

    abstract::Epithelial-mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%-30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic in...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Wong CE,Yu JS,Quigley DA,To MD,Jen KY,Huang PY,Del Rosario R,Balmain A

    更新日期:2013-03-15 00:00:00

  • Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4.

    abstract::Histone deacetylase 3 (HDAC3) is one of four members of the human class I HDACs that regulates gene expression by deacetylation of histones and nonhistone proteins. Early studies have suggested that HDAC3 activity is regulated by association with the corepressors N-CoR and SMRT. Here we demonstrate that, in addition t...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Zhang X,Ozawa Y,Lee H,Wen YD,Tan TH,Wadzinski BE,Seto E

    更新日期:2005-04-01 00:00:00

  • CBL family E3 ubiquitin ligases control JAK2 ubiquitination and stability in hematopoietic stem cells and myeloid malignancies.

    abstract::Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (C...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Lv K,Jiang J,Donaghy R,Riling CR,Cheng Y,Chandra V,Rozenova K,An W,Mohapatra BC,Goetz BT,Pillai V,Han X,Todd EA,Jeschke GR,Langdon WY,Kumar S,Hexner EO,Band H,Tong W

    更新日期:2017-05-15 00:00:00

  • The role of disordered protein regions in the assembly of decapping complexes and RNP granules.

    abstract::The removal of the 5' cap structure by the decapping enzyme DCP2 inhibits translation and generally commits the mRNA to irreversible 5'-to-3' exonucleolytic degradation by XRN1. DCP2 catalytic activity is stimulated by DCP1, and these proteins form the conserved core of the decapping complex. Additional decapping fact...

    journal_title:Genes & development

    pub_type: 杂志文章,评审


    authors: Jonas S,Izaurralde E

    更新日期:2013-12-15 00:00:00

  • Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses.

    abstract::Placental development is profoundly influenced by oxygen (O(2)) tension. Human cytotrophoblasts proliferate in vitro under low O(2) conditions but differentiate at higher O(2) levels, mimicking the developmental transition they undergo as they invade the placental bed to establish the maternal-fetal circulation in viv...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Adelman DM,Gertsenstein M,Nagy A,Simon MC,Maltepe E

    更新日期:2000-12-15 00:00:00

  • The dishevelled protein is modified by wingless signaling in Drosophila.

    abstract::Wingless (Wg) is an important signaling molecule in the development of Drosophila, but little is known about its signal transduction pathway. Genetic evidence indicates that another segment polarity gene, dishevelled (dsh) is required for Wg signaling. We have recently developed a cell culture system for Wg protein ac...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Yanagawa S,van Leeuwen F,Wodarz A,Klingensmith J,Nusse R

    更新日期:1995-05-01 00:00:00

  • In vivo analysis of the helix-turn-helix motif of the fushi tarazu homeo domain of Drosophila melanogaster.

    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


    authors: Furukubo-Tokunaga K,Müller M,Affolter M,Pick L,Kloter U,Gehring WJ

    更新日期:1992-06-01 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


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

    更新日期:2004-01-15 00:00:00

  • HFR1 is targeted by COP1 E3 ligase for post-translational proteolysis during phytochrome A signaling.

    abstract::Upon activation by far-red light, phytochrome A signals are transduced through several pathways to promote photomorphogenesis. The COP1 E3 ligase represses photomorphogenesis in part by targeting transcription activators such as LAF1 and HY5 for destruction. Another positive regulator of photomorphogenesis is HFR1, a ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Jang IC,Yang JY,Seo HS,Chua NH

    更新日期:2005-03-01 00:00:00

  • The block to transcriptional elongation within the human c-myc gene is determined in the promoter-proximal region.

    abstract::A conditional block to transcriptional elongation is an important mechanism for regulating c-myc gene expression. This elongation block within the first c-myc exon was defined originally in mammalian cells by nuclear run-on transcription analyses. Subsequent oocyte injection and in vitro transcription analyses suggest...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Krumm A,Meulia T,Brunvand M,Groudine M

    更新日期:1992-11-01 00:00:00

  • Cooperative recruitment of Yan via a high-affinity ETS supersite organizes repression to confer specificity and robustness to cardiac cell fate specification.

    abstract::Cis-regulatory modules (CRMs) are defined by unique combinations of transcription factor-binding sites. Emerging evidence suggests that the number, affinity, and organization of sites play important roles in regulating enhancer output and, ultimately, gene expression. Here, we investigate how the cis-regulatory logic ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Boisclair Lachance JF,Webber JL,Hong L,Dinner AR,Rebay I

    更新日期:2018-03-01 00:00:00

  • A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo.

    abstract::Translation initiation factor 2 (eIF2) bound to GTP transfers the initiator methionyl tRNA to the 40S ribosomal subunit. The eIF5 stimulates GTP hydrolysis by the eIF2/GTP/Met-tRNA(i)(Met) ternary complex on base-pairing between Met-tRNA(i)(Met) and the start codon. The eIF2, eIF5, and eIF1 all have been implicated in...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Asano K,Clayton J,Shalev A,Hinnebusch AG

    更新日期:2000-10-01 00:00:00

  • Breaking down bone: new insight into site-specific mechanisms of breast cancer osteolysis mediated by metalloproteinases.

    abstract::Bone metastases are the most common skeletal complication of malignancy. Tumor cells disrupt normal bone remodeling to promote bone destruction and its associated morbidity. In the August 15, 2009, issue of Genes & Development, Lu and colleagues (pp. 1882-1894) propose a novel molecular mechanism by which tumor-produc...

    journal_title:Genes & development

    pub_type: 评论,杂志文章


    authors: Guise TA

    更新日期:2009-09-15 00:00:00

  • Dual mechanisms prevent premature chromosome segregation during meiosis.

    abstract::In meiosis I, homologous chromosomes pair and then attach to the spindle so that the homologs can be pulled apart at anaphase I. The segregation of homologs before pairing would be catastrophic. We describe two mechanisms that prevent this. First, in early meiosis, Ipl1, the budding yeast homolog of the mammalian Auro...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Kim S,Meyer R,Chuong H,Dawson DS

    更新日期:2013-10-01 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


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

    更新日期:1995-08-01 00:00:00

  • Error-free replicative bypass of (6-4) photoproducts by DNA polymerase zeta in mouse and human cells.

    abstract::The ultraviolet (UV)-induced (6-4) pyrimidine-pyrimidone photoproduct [(6-4) PP] confers a large structural distortion in DNA. Here we examine in human cells the roles of translesion synthesis (TLS) DNA polymerases (Pols) in promoting replication through a (6-4) TT photoproduct carried on a duplex plasmid where bidire...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Yoon JH,Prakash L,Prakash S

    更新日期:2010-01-15 00:00:00

  • Diverse protein kinase interactions identified by protein microarrays reveal novel connections between cellular processes.

    abstract::Protein kinases are key regulators of cellular processes. In spite of considerable effort, a full understanding of the pathways they participate in remains elusive. We globally investigated the proteins that interact with the majority of yeast protein kinases using protein microarrays. Eighty-five kinases were purifie...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Fasolo J,Sboner A,Sun MG,Yu H,Chen R,Sharon D,Kim PM,Gerstein M,Snyder M

    更新日期:2011-04-01 00:00:00

  • The excess microsporocytes1 gene encodes a putative leucine-rich repeat receptor protein kinase that controls somatic and reproductive cell fates in the Arabidopsis anther.

    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


    authors: Zhao DZ,Wang GF,Speal B,Ma H

    更新日期:2002-08-01 00:00:00

  • A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans.

    abstract::An insulin receptor-like signaling pathway regulates Caenorhabditis elegans metabolism, development, and longevity. Inactivation of the insulin receptor homolog DAF-2, the AGE-1 PI3K, or the AKT-1 and AKT-2 kinases causes a developmental arrest at the dauer stage. A null mutation in the daf-16 Fork head transcription ...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Paradis S,Ailion M,Toker A,Thomas JH,Ruvkun G

    更新日期:1999-06-01 00:00:00

  • Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase.

    abstract::The serine/threonine kinase Akt/PKB is a major downstream effector of growth factor-mediated cell survival. Activated Akt, like Bcl-2 and Bcl-xL, prevents closure of a PT pore component, the voltage-dependent anion channel (VDAC); intracellular acidification; mitochondrial hyperpolarization; and the decline in oxidati...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Gottlob K,Majewski N,Kennedy S,Kandel E,Robey RB,Hay N

    更新日期:2001-06-01 00:00:00

  • PPARγ is a nexus controlling alternative activation of macrophages via glutamine metabolism.

    abstract::The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that peritoneal macrophage respiration is enhanced by rosiglitazone, an activating PPARγ ligand, in a PPARγ-dependent manner. Moreover, PPARγ is require...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Nelson VL,Nguyen HCB,Garcìa-Cañaveras JC,Briggs ER,Ho WY,DiSpirito JR,Marinis JM,Hill DA,Lazar MA

    更新日期:2018-08-01 00:00:00

  • Yeast calcineurin regulates nuclear localization of the Crz1p transcription factor through dephosphorylation.

    abstract::Calcineurin, a Ca2+/calmodulin dependent protein phosphatase, regulates Ca2+-dependent processes in a wide variety of cells. In the yeast, Saccharomyces cerevisiae, calcineurin effects Ca2+-dependent changes in gene expression through regulation of the Crz1p transcription factor. We show here that calcineurin dephosph...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Stathopoulos-Gerontides A,Guo JJ,Cyert MS

    更新日期:1999-04-01 00:00:00

  • Different upstream transcriptional activators have distinct coactivator requirements.

    abstract::Activated transcription by RNA polymerase II (Pol II) requires coactivators, one of which is the SRB/mediator. Whereas Srb4, an essential subunit of the SRB/mediator, is broadly required for Pol II transcription in yeast, we have shown that it is dispensable for the transcriptional activation of some genes. Here, we s...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Lee DK,Kim S,Lis JT

    更新日期:1999-11-15 00:00:00

  • Topoisomerases and yeast rRNA transcription: negative supercoiling stimulates initiation and topoisomerase activity is required for elongation.

    abstract::Previous work has shown that rRNA synthesis is strongly inhibited in yeast top1-top2 double mutants. Here, we show that inactivation of yeast topoisomerases can have paradoxical effects on transcription by RNA polymerase I. For example, transcription of ribosomal minigenes on extrachromosomal plasmids is greatly stimu...

    journal_title:Genes & development

    pub_type: 杂志文章


    authors: Schultz MC,Brill SJ,Ju Q,Sternglanz R,Reeder RH

    更新日期:1992-07-01 00:00:00