Oncogenic Ras activation of Raf/mitogen-activated protein kinase-independent pathways is sufficient to cause tumorigenic transformation.

Abstract:

:Substantial evidence supports a critical role for the activation of the Raf-1/MEK/mitogen-activated protein kinase pathway in oncogenic Ras-mediated transformation. For example, dominant negative mutants of Raf-1, MEK, and mitogen-activated protein kinase all inhibit Ras transformation. Furthermore, the observation that plasma membrane-localized Raf-1 exhibits the same transforming potency as oncogenic Ras suggests that Raf-1 activation alone is sufficient to mediate full Ras transforming activity. However, the recent identification of other candidate Ras effectors (e.g., RalGDS and phosphatidylinositol-3 kinase) suggests that activation of other downstream effector-mediated signaling pathways may also mediate Ras transforming activity. In support of this, two H-Ras effector domain mutants, H-Ras(12V, 37G) and H-Ras(12V, 40C), which are defective for Raf binding and activation, induced potent tumorigenic transformation of some strains of NIH 3T3 fibroblasts. These Raf-binding defective mutants of H-Ras induced a transformed morphology that was indistinguishable from that induced by activated members of Rho family proteins. Furthermore, the transforming activities of both of these mutants were synergistically enhanced by activated Raf-1 and inhibited by the dominant negative RhoA(19N) mutant, indicating that Ras may cause transformation that occurs via coordinate activation of Raf-dependent and -independent pathways that involves Rho family proteins. Finally, cotransfection of H-Ras(12V, 37G) and H-Ras(12V, 40C) resulted in synergistic cooperation of their focus-forming activities, indicating that Ras activates at least two Raf-independent, Ras effector-mediated signaling events.

journal_name

Mol Cell Biol

authors

Khosravi-Far R,White MA,Westwick JK,Solski PA,Chrzanowska-Wodnicka M,Van Aelst L,Wigler MH,Der CJ

doi

10.1128/mcb.16.7.3923

subject

Has Abstract

pub_date

1996-07-01 00:00:00

pages

3923-33

issue

7

eissn

0270-7306

issn

1098-5549

journal_volume

16

pub_type

杂志文章
  • Redistribution of activated pp60c-src to integrin-dependent cytoskeletal complexes in thrombin-stimulated platelets.

    abstract::Thrombin stimulation of platelets induces a transient increase in the specific activity of pp60c-src followed by a redistribution of pp60c-src to the Triton X-100-insoluble, cytoskeleton-rich fraction. Concomitant with the observed increase in pp60c-src activity was a rapid dephosphorylation of tyrosine 527 in 10 to 1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.3.1863

    authors: Clark EA,Brugge JS

    更新日期:1993-03-01 00:00:00

  • Cdc1p is an endoplasmic reticulum-localized putative lipid phosphatase that affects Golgi inheritance and actin polarization by activating Ca2+ signaling.

    abstract::In the budding yeast Saccharomyces cerevisiae, mutations in the essential gene CDC1 cause defects in Golgi inheritance and actin polarization. However, the biochemical function of Cdc1p is unknown. Previous work showed that cdc1 mutants accumulate intracellular Ca(2+) and display enhanced sensitivity to the extracellu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00567-07

    authors: Losev E,Papanikou E,Rossanese OW,Glick BS

    更新日期:2008-05-01 00:00:00

  • Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation.

    abstract::The human 4F2 cell surface antigen is a 120-kilodalton (kDa) disulfide-linked heterodimer which is composed of an 80- to 90-kDa glycosylated heavy chain (4F2HC) and a 35- to 40-kDa nonglycosylated light chain (4F2LC). 4F2 belongs to a family of inducible cell surface molecules which are involved in T-lymphocyte activa...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.9.3809

    authors: Gottesdiener KM,Karpinski BA,Lindsten T,Strominger JL,Jones NH,Thompson CB,Leiden JM

    更新日期:1988-09-01 00:00:00

  • La-related protein 4 binds poly(A), interacts with the poly(A)-binding protein MLLE domain via a variant PAM2w motif, and can promote mRNA stability.

    abstract::The conserved RNA binding protein La recognizes UUU-3'OH on its small nuclear RNA ligands and stabilizes them against 3'-end-mediated decay. We report that newly described La-related protein 4 (LARP4) is a factor that can bind poly(A) RNA and interact with poly(A) binding protein (PABP). Yeast two-hybrid analysis and ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01162-10

    authors: Yang R,Gaidamakov SA,Xie J,Lee J,Martino L,Kozlov G,Crawford AK,Russo AN,Conte MR,Gehring K,Maraia RJ

    更新日期:2011-02-01 00:00:00

  • 5'-flanking sequence required for regulated expression of a muscle-specific Drosophila melanogaster actin gene.

    abstract::We have functionally tested derivatives of a muscle-specific Drosophila melanogaster actin gene in which 5'-flanking sequences have been deleted or rearranged. From our results we conclude that approximately 1,000 nucleotides of 5'-flanking sequence are required for wild-type levels of mRNA accumulation during flight ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.10.3388

    authors: Geyer PK,Fyrberg EA

    更新日期:1986-10-01 00:00:00

  • E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation.

    abstract::Within mineralized bone, osteocytes form dendritic processes that travel through canaliculi to make contact with other osteocytes and cells on the bone surface. This three-dimensional syncytium is thought to be necessary to maintain viability, cell-to-cell communication, and mechanosensation. E11/gp38 is the earliest ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.02120-05

    authors: Zhang K,Barragan-Adjemian C,Ye L,Kotha S,Dallas M,Lu Y,Zhao S,Harris M,Harris SE,Feng JQ,Bonewald LF

    更新日期:2006-06-01 00:00:00

  • Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2.

    abstract::The product of the c-myc proto-oncogene is an important positive regulator of cell growth and proliferation. Recently, c-Myc has also been demonstrated to be a potent inducer of apoptosis when expressed in the absence of serum or growth factors. To further examine Myc-induced apoptosis, we coexpressed the proto-oncoge...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.4.2432

    authors: Wagner AJ,Small MB,Hay N

    更新日期:1993-04-01 00:00:00

  • HTL1 encodes a novel factor that interacts with the RSC chromatin remodeling complex in Saccharomyces cerevisiae.

    abstract::RSC is an essential chromatin remodeling complex in Saccharomyces cerevisiae that performs central roles in transcriptional regulation and cell cycle progression. Here we identify Htl1 as a novel factor that associates with the RSC complex both physically and functionally. We isolated HTL1 through a genetic screen for...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.23.8165-8174.2002

    authors: Romeo MJ,Angus-Hill ML,Sobering AK,Kamada Y,Cairns BR,Levin DE

    更新日期:2002-12-01 00:00:00

  • RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization.

    abstract::Mitogen activation of mRNA decay pathways likely involves specific endoribonucleases, such as G3BP, a phosphorylation-dependent endoribonuclease that associates with RasGAP in dividing but not quiescent cells. G3BP exclusively cleaves between cytosine and adenine (CA) after a specific interaction with RNA through the ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.22.7747-7760.2001

    authors: Tourrière H,Gallouzi IE,Chebli K,Capony JP,Mouaikel J,van der Geer P,Tazi J

    更新日期:2001-11-01 00:00:00

  • Promoter and enhancer elements from the rat elastase I gene function independently of each other and of heterologous enhancers.

    abstract::An elastase-human growth hormone (hGH) fusion gene containing 205 base pairs of elastase 5' flanking region is expressed exclusively in pancreatic acinar cells of transgenic mice. This paper shows that the promoter region (-72 to +8) and the enhancer (-205 to -73) function independently of each other. The elastase enh...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.10.3466

    authors: Ornitz DM,Hammer RE,Davison BL,Brinster RL,Palmiter RD

    更新日期:1987-10-01 00:00:00

  • Assembly of a tRNA splicing complex: evidence for concerted excision and joining steps in splicing in vitro.

    abstract::Splicing of tRNA precursors in Saccharomyces cerevisiae extracts proceeds in two steps; excision of the intervening sequence and ligation of the tRNA halves. The ability to resolve these two steps and the distinct physical properties of the endonuclease and ligase suggested that the splicing steps may not be concerted...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.2.635

    authors: Greer CL

    更新日期:1986-02-01 00:00:00

  • The highly conserved beta-hairpin of the paired DNA-binding domain is required for assembly of Pax-Ets ternary complexes.

    abstract::Pax family transcription factors bind DNA through the paired domain. This domain, which is comprised of two helix-turn-helix motifs and a beta-hairpin structure, is a target of mutations in congenital disorders of mice and humans. Previously, we showed that Pax-5 (B-cell-specific activator protein) recruits proteins o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.3.2231

    authors: Wheat W,Fitzsimmons D,Lennox H,Krautkramer SR,Gentile LN,McIntosh LP,Hagman J

    更新日期:1999-03-01 00:00:00

  • Overexpression of HOXA10 in murine hematopoietic cells perturbs both myeloid and lymphoid differentiation and leads to acute myeloid leukemia.

    abstract::Multiple members of the A, B, and C clusters of Hox genes are expressed in hematopoietic cells. Several of these Hox genes have been found to display distinctive expression patterns, with genes located at the 3' side of the clusters being expressed at their highest levels in the most primitive subpopulation of human C...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.1.495

    authors: Thorsteinsdottir U,Sauvageau G,Hough MR,Dragowska W,Lansdorp PM,Lawrence HJ,Largman C,Humphries RK

    更新日期:1997-01-01 00:00:00

  • Dynamic histone variant exchange accompanies gene induction in T cells.

    abstract::Changes in chromatin composition are often a prerequisite for gene induction. Nonallelic histone variants have recently emerged as key players in transcriptional control and chromatin modulation. While the changes in chromatin accessibility and histone posttranslational modification (PTM) distribution that accompany g...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01590-08

    authors: Sutcliffe EL,Parish IA,He YQ,Juelich T,Tierney ML,Rangasamy D,Milburn PJ,Parish CR,Tremethick DJ,Rao S

    更新日期:2009-04-01 00:00:00

  • Farnesoid X receptor inhibits the transcriptional activity of carbohydrate response element binding protein in human hepatocytes.

    abstract::The glucose-activated transcription factor carbohydrate response element binding protein (ChREBP) induces the expression of hepatic glycolytic and lipogenic genes. The farnesoid X receptor (FXR) is a nuclear bile acid receptor controlling bile acid, lipid, and glucose homeostasis. FXR negatively regulates hepatic glyc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01004-12

    authors: Caron S,Huaman Samanez C,Dehondt H,Ploton M,Briand O,Lien F,Dorchies E,Dumont J,Postic C,Cariou B,Lefebvre P,Staels B

    更新日期:2013-06-01 00:00:00

  • Inhibition of E2F activity by the cyclin-dependent protein kinase inhibitor p21 in cells expressing or lacking a functional retinoblastoma protein.

    abstract::p21Sdi1/WAF1/Cip1 inhibits cyclin-dependent protein kinases and cell proliferation. p21 is presumed to inhibit growth by preventing the phosphorylation of growth-regulatory proteins, including the retinoblastoma tumor suppressor protein (pRb). The ultimate effector(s) of p21 growth inhibition, however, is largely a ma...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.6.2987

    authors: Dimri GP,Nakanishi M,Desprez PY,Smith JR,Campisi J

    更新日期:1996-06-01 00:00:00

  • Endothelial cytosolic proteins bind to the 3' untranslated region of endothelial nitric oxide synthase mRNA: regulation by tumor necrosis factor alpha.

    abstract::Changes in endothelial nitric oxide synthase (eNOS) expression may be involved in the endothelium-dependent vasorelaxation dysfunction associated with several vascular diseases. In the present work, we demonstrate that eNOS mRNA contains a previously undescribed cis element in the 3' untranslated region (3' UTR). A U+...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.10.5719

    authors: Alonso J,Sánchez de Miguel L,Montón M,Casado S,López-Farré A

    更新日期:1997-10-01 00:00:00

  • A Heterologous Cell Model for Studying the Role of T-Cell Intracellular Antigen 1 in Welander Distal Myopathy.

    abstract::Welander distal myopathy (WDM) is a muscle dystrophy characterized by adult-onset distal muscle weakness, prevalently impacting the distal long extensors of the hands and feet. WDM is an autosomal dominant disorder caused by a missense mutation (c.1362G>A; p.E384K) in the TIA1 (T-cell intracellular antigen 1) gene, wh...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00299-18

    authors: Carrascoso I,Sánchez-Jiménez C,Silion E,Alcalde J,Izquierdo JM

    更新日期:2018-12-11 00:00:00

  • c-Myc is necessary for DNA damage-induced apoptosis in the G(2) phase of the cell cycle.

    abstract::The c-myc proto-oncogene encodes a transcription factor that participates in the regulation of cellular proliferation, differentiation, and apoptosis. Ectopic overexpression of c-Myc has been shown to sensitize cells to apoptosis. We report here that cells lacking c-Myc activity due to disruption of the c-myc gene by ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.15.4929-4937.2001

    authors: Adachi S,Obaya AJ,Han Z,Ramos-Desimone N,Wyche JH,Sedivy JM

    更新日期:2001-08-01 00:00:00

  • Glycosylation and secretion of human tissue plasminogen activator in recombinant baculovirus-infected insect cells.

    abstract::Cell lines established from the lepidopteran insect Spodoptera frugiperda (fall armyworm; Sf9) are used routinely as hosts for the expression of foreign proteins by recombinant baculovirus vectors. We have examined the pathway of protein glycosylation and secretion in these cells, using human tissue plasminogen activa...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.1.214

    authors: Jarvis DL,Summers MD

    更新日期:1989-01-01 00:00:00

  • A Repertoire of MicroRNAs Regulates Cancer Cell Starvation by Targeting Phospholipase D in a Feedback Loop That Operates Maximally in Cancer Cells.

    abstract::We report a negative feedback loop between the signaling protein phospholipase D (PLD), phosphatidic acid (PA), and a specific set of microRNAs (miRNAs) during nutrient starvation of breast cancer cells. We show that PLD expression is increased in four breast cancer cell lines and that hypoxia, cell overcrowding, and ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00711-15

    authors: Fite K,Elkhadragy L,Gomez-Cambronero J

    更新日期:2016-01-19 00:00:00

  • Long-range RNA interaction of two sequence elements required for endonucleolytic cleavage of human insulin-like growth factor II mRNAs.

    abstract::Human insulin-like growth factor II (IGF-II) mRNAs are subject to site-specific endonucleolytic cleavage in the 3' untranslated region, leading to an unstable 5' cleavage product containing the IGF-II coding region and a very stable 3' cleavage product of 1.8 kb. This endonucleolytic cleavage is most probably the firs...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.1.235

    authors: Scheper W,Meinsma D,Holthuizen PE,Sussenbach JS

    更新日期:1995-01-01 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

    doi:10.1128/mcb.3.8.1371

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

    更新日期:1983-08-01 00:00:00

  • Gata4 regulates testis expression of Dmrt1.

    abstract::The doublesex and mab-3 related transcription factor 1 (Dmrt1) is a putative transcriptional regulator that is expressed exclusively in the gonads and is required for postnatal testis differentiation. Here we describe the transcriptional mechanisms regulating testis-specific expression of the Dmrt1 gene. Transient-tra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.1.377-388.2004

    authors: Lei N,Heckert LL

    更新日期:2004-01-01 00:00:00

  • Activation of protein kinase C triggers its ubiquitination and degradation.

    abstract::Treatment of cells with tumor-promoting phorbol esters results in the activation but then depletion of phorbol ester-responsive protein kinase C (PKC) isoforms. The ubiquitin-proteasome pathway has been implicated in regulating the levels of many cellular proteins, including those involved in cell cycle control. We re...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.2.839

    authors: Lu Z,Liu D,Hornia A,Devonish W,Pagano M,Foster DA

    更新日期:1998-02-01 00:00:00

  • Characterization of a telomere-binding protein from Physarum polycephalum.

    abstract::We have partially purified a nuclear protein (PPT) from Physarum polycephalum that binds to the extrachromosomal ribosomal DNA telomeres of this acellular slime mold. Binding is specific for the (T2AG3)n telomere repeats, as evidenced by nitrocellulose filter binding assays, by gel mobility shift assays with both DNA ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.4.2282

    authors: Coren JS,Epstein EM,Vogt VM

    更新日期:1991-04-01 00:00:00

  • Interleukin-6-induced STAT3 and AP-1 amplify hepatocyte nuclear factor 1-mediated transactivation of hepatic genes, an adaptive response to liver injury.

    abstract::Following hepatic injury or stress, gluconeogenic and acute-phase response genes are rapidly upregulated to restore metabolic homeostasis and limit tissue damage. Regulation of the liver-restricted insulin-like growth factor binding protein 1 (IGFBP-1) gene is dramatically altered by changes in the metabolic state and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.2.414-424.2001

    authors: Leu JI,Crissey MA,Leu JP,Ciliberto G,Taub R

    更新日期:2001-01-01 00:00:00

  • A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1.

    abstract::The tumor suppressor WT1 represses and activates transcription. The loss and/or imbalance of the dual transcriptional activity of WT1 may contribute to Wilms' tumor. In this study, we identified par-4 (for prostate apoptosis response) as a WT1-interacting protein that itself functions as a transcriptional repressor. p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.12.6945

    authors: Johnstone RW,See RH,Sells SF,Wang J,Muthukkumar S,Englert C,Haber DA,Licht JD,Sugrue SP,Roberts T,Rangnekar VM,Shi Y

    更新日期:1996-12-01 00:00:00

  • Hematopoietic cell fate and the initiation of leukemic properties in primitive primary human cells are influenced by Ras activity and farnesyltransferase inhibition.

    abstract::The Ras pathway transduces divergent signals determining normal cell fate and is frequently activated in hematopoietic malignancies, but the manner in which activation contributes to human leukemia is poorly understood. We report that a high level of activated H-Ras signaling in transduced primary human hematopoietic ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.16.6993-7002.2004

    authors: Dorrell C,Takenaka K,Minden MD,Hawley RG,Dick JE

    更新日期:2004-08-01 00:00:00

  • The role of Djp1 in import of the mitochondrial protein Mim1 demonstrates specificity between a cochaperone and its substrate protein.

    abstract::A special group of mitochondrial outer membrane proteins spans the membrane once, exposing soluble domains to both sides of the membrane. These proteins are synthesized in the cytosol and then inserted into the membrane by an unknown mechanism. To identify proteins that are involved in the biogenesis of the single-spa...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00227-13

    authors: Papić D,Elbaz-Alon Y,Koerdt SN,Leopold K,Worm D,Jung M,Schuldiner M,Rapaport D

    更新日期:2013-10-01 00:00:00