Abstract:
:Ras GTPases were long thought to function exclusively from the plasma membrane (PM). However, a current model suggests that Ras proteins can compartmentalize to regulate different functions, and an oncogenic H-Ras mutant that is restricted to the endomembrane can still transform cells. In this study, we demonstrated that cells transformed by endomembrane-restricted oncogenic H-Ras formed tumors in nude mice. To define downstream targets of endomembrane Ras pathways, we analyzed Cdc42, which concentrates in the endomembrane and has been shown to act downstream of Ras in Schizosaccharomyces pombe. Our data show that cell transformation induced by endomembrane-restricted oncogenic H-Ras was blocked when Cdc42 activity was inhibited. Moreover, H-Ras formed a complex with Cdc42 on the endomembrane, and this interaction was enhanced when H-Ras was GTP bound or when cells were stimulated by growth factors. H-Ras binding evidently induced Cdc42 activation by recruiting and/or activating Cdc42 exchange factors. In contrast, when constitutively active H-Ras was restricted to the PM by fusing to a PM localization signal from the Rit GTPase, the resulting protein did not detectably activate Cdc42 although it activated Raf-1 and efficiently induced hallmarks of Ras-induced senescence in human BJ foreskin fibroblasts. Surprisingly, PM-restricted oncogenic Ras when expressed alone could only weakly transform NIH 3T3 cells; however, when constitutively active Cdc42 was coexpressed, together they transformed cells much more efficiently than either one alone. These data suggest that efficient cell transformation requires Ras proteins to interact with Cdc42 on the endomembrane and that in order for a given Ras protein to fully transform cells, multiple compartment-specific Ras pathways need to work cooperatively.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Cheng CM,Li H,Gasman S,Huang J,Schiff R,Chang ECdoi
10.1128/MCB.00137-10subject
Has Abstractpub_date
2011-03-01 00:00:00pages
983-97issue
5eissn
0270-7306issn
1098-5549pii
MCB.00137-10journal_volume
31pub_type
杂志文章abstract::Hybridization to synthetic oligonucleotides representing conserved regions in the promoter and first intron of several vertebrate beta-actin genes was used to discriminate between what appears to be a single functional beta-actin gene and numerous pseudogenes in the mouse genome. Sequences derived from the 5' end of t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.1.480
更新日期:1988-01-01 00:00:00
abstract::Members of the cytokine receptor superfamily have structurally similar extracellular ligand-binding domains yet diverse cytoplasmic regions lacking any obvious catalytic domains. Many of these receptors form ligand-induced oligomers which are likely to participate in transmembrane signaling. A constitutively active (f...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.3535
更新日期:1994-06-01 00:00:00
abstract::The death-associated protein (DAP) kinase family includes three protein kinases, DAP kinase, DAP kinase-related protein 1, and ZIP kinase, which display 80% amino acid identity within their catalytic domains and are functionally linked to common subcellular changes occurring during cell death, such as the process of m...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.19.8611-8626.2004
更新日期:2004-10-01 00:00:00
abstract::The cytokine gamma interferon (IFN-gamma) and the calcitropic steroid hormone 1,25-dihydroxyvitamin D (1,25D) are activators of macrophage immune function. In sarcoidosis, tuberculosis, and several granulomatoses, IFN-gamma induces 1,25D synthesis by macrophages and inhibits 1,25D induction of 24-hydroxylase, a key en...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.8.2777-2787.2002
更新日期:2002-04-01 00:00:00
abstract::ATR kinase activation requires the recruitment of the ATR-ATRIP and RAD9-HUS1-RAD1 (9-1-1) checkpoint complexes to sites of DNA damage or replication stress. Replication protein A (RPA) bound to single-stranded DNA is at least part of the molecular recognition element that recruits these checkpoint complexes. We have ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01079-08
更新日期:2008-12-01 00:00:00
abstract::The Tor pathway mediates cell growth in response to nutrient availability, in part by inducing ribosomal protein (RP) gene expression via an unknown mechanism. Expression of RP genes coincides with recruitment of the Esa1 histone acetylase to RP gene promoters. We show that inhibition of Tor with rapamycin releases Es...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.2.629-635.2003
更新日期:2003-01-01 00:00:00
abstract::Schizosaccharomyces pombe Cdc5p and its Saccharomyces cerevisiae ortholog, Cef1p, are essential Myb-related proteins implicated in pre-mRNA splicing and contained within large multiprotein complexes. Here we describe the tandem affinity purification (TAP) of Cdc5p- and Cef1p-associated complexes. Using transmission el...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.7.2011-2024.2002
更新日期:2002-04-01 00:00:00
abstract::The transcriptional factor Snail1 is a repressor of E-cadherin (CDH1) gene expression essential for triggering epithelial-mesenchymal transition. Snail1 represses CDH1, directly binding its promoter and inducing the synthesis of the Zeb1 repressor. In this article, we show that repression of CDH1 by Snail1, but not by...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00323-08
更新日期:2008-08-01 00:00:00
abstract::Rad53 of Saccharomyces cerevisiae is a checkpoint kinase whose structure and function are conserved among eukaryotes. When a cell detects damaged DNA, Rad53 activity is dramatically increased, which ultimately leads to changes in DNA replication, repair, and cell division. Despite its central role in checkpoint signal...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.10.3405-3416.2003
更新日期:2003-05-01 00:00:00
abstract::The transcriptional coactivator Cbp plays an important role in a wide range of cellular processes, including proliferation, differentiation, and apoptosis. Although studies have shown its requirement for hematopoietic stem cell (HSC) development, its role in adult HSC maintenance, as well as the cellular and molecular...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05830-11
更新日期:2011-12-01 00:00:00
abstract::In eukaryotic cells, calcium entry across the cell surface activates nuclear gene expression, a process critically important for cell growth and differentiation, learning, and memory and immune cell functions. In immune cells, calcium entry occurs through store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01068-14
更新日期:2015-04-01 00:00:00
abstract::zfh-1 is a member of the zfh family of proteins, which all contain zinc finger and homeodomains. The roles and mechanisms of action of most family members are still unclear. However, we have shown previously that another member of the family, the vertebrate ZEB protein, is a transcriptional repressor that binds E box ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.7255
更新日期:1999-10-01 00:00:00
abstract::The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is an important regulator of cell cycle progression, senescence, and differentiation. Genotoxic stress leads to activation of the tumor suppressor p53 and subsequently to induction of p21 expression. Here we show that the tumor suppressor p53 cooperates with the tran...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.8.2669-2679.2003
更新日期:2003-04-01 00:00:00
abstract::PHAX (phosphorylated adaptor for RNA export) is the key regulator of U snRNA nuclear export in metazoa. Our previous work revealed that PHAX is phosphorylated in the nucleus and is exported as a component of the U snRNA export complex to the cytoplasm, where it is dephosphorylated (M. Ohno, A. Segref, A. Bachi, M. Wil...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01189-07
更新日期:2008-01-01 00:00:00
abstract::We report here the isolation of a novel, highly tissue-restricted member of the ets transcription factor/oncogene family, ESE-1 (for epithelium-specific Ets), which has features distinct from those of any other ets-related factor. ESE-1 contains two putative DNA binding domains: an ETS domain, which is unique in that ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.8.4419
更新日期:1997-08-01 00:00:00
abstract::To identify novel genes that play critical roles in mediating bone morphogenetic protein (BMP) signal pathways, we performed a yeast two-hybrid screen using Smad1 as bait. A novel mouse Krüppel-type zinc finger protein, mZnf8, was isolated. Interactions between mZnf8 and Smad proteins were further analyzed with variou...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.21.7633-7644.2002
更新日期:2002-11-01 00:00:00
abstract::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 st...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00699-08
更新日期:2009-01-01 00:00:00
abstract::Tumor-promoting phorbol esters affect a variety of cellular functions which may underlie tumor promotion. We isolated from human lymphocytes a cDNA clone whose gene is inducible by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate as well as by the T-cell mitogen phytohemagglutinin. Nuclear transcription experim...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.11.2540
更新日期:1984-11-01 00:00:00
abstract::Telomere maintenance is required for chromosome stability, and telomeres are typically replicated by the action of the reverse transcriptase telomerase. In both tumor and yeast cells that lack telomerase, telomeres are maintained by an alternative recombination mechanism. Genetic studies have led to the identification...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.16.5679-5687.2002
更新日期:2002-08-01 00:00:00
abstract::The full-length versions of the Ras-specific exchange factors Ras-GRF1 (GRF1) and Ras-GRF2 (GRF2), which are expressed in brain and a restricted number of other organs, possess an ionomycin-dependent activation of Erk mitogen-activated protein kinase activity in 293T cells (C. L. Farnsworth et al., Nature 376:524-527,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.7.4611
更新日期:1999-07-01 00:00:00
abstract::The mammalian double-stranded RNA-activated protein kinase PKR is a component of the cellular antiviral defense mechanism and phosphorylates Ser-51 on the alpha subunit of the translation factor eIF2 to inhibit protein synthesis. To identify the molecular determinants that specify substrate recognition by PKR, we perf...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.7.4146
更新日期:1997-07-01 00:00:00
abstract::The ribonucleoprotein enzyme telomerase is a specialized reverse transcriptase that synthesizes telomeric DNA by copying a template sequence within the telomerase RNA. Here we analyze the actions of telomerase from Tetrahymena thermophila assembled in vivo with mutated or wild-type telomerase RNA to define further the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.1.66
更新日期:1996-01-01 00:00:00
abstract::Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney, and a deficiency of this protein results in multiple rena...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00392-12
更新日期:2012-12-01 00:00:00
abstract::Fragile X syndrome, the most common form of hereditary mental retardation, usually results from lack of expression of the FMR1 gene. The FMR1 protein is a cytoplasmic RNA-binding protein. The RNA-binding activity of FMR1 is an essential feature of FMR1, as fragile X syndrome can also result from the expression of muta...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.7.3825
更新日期:1996-07-01 00:00:00
abstract::SEC63 encodes a protein required for secretory protein translocation into the endoplasmic reticulum (ER) of Saccharomyces cerevisiae (J. A. Rothblatt, R. J. Deshaies, S. L. Sanders, G. Daum, and R. Schekman, J. Cell Biol. 109:2641-2652, 1989). Antibody directed against a recombinant form of the protein detects a 73-kD...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.7.3288
更新日期:1992-07-01 00:00:00
abstract::In roughly 5% of cases of acute lymphoblastic leukemia, a chromosomal translocation leads to expression of the oncogenic protein E2A-PBX1. The N-terminal portion of E2A-PBX1, encoded by the E2A gene, is identical in sequence to the corresponding portion of the E proteins E12/E47 and includes transcriptional activation...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02025-05
更新日期:2006-09-01 00:00:00
abstract::Cell polarity plays a critical role in the development of all metazoans; however, the mechanisms of cell polarity and the specific role of cell polarity pathways in mammalian organisms are still poorly understood. Lethal giant larvae (Lgl) is an apical-basal polarity gene identified in Drosophila, where it functions a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05431-11
更新日期:2011-07-01 00:00:00
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
doi:10.1128/MCB.25.10.4321-4332.2005
更新日期:2005-05-01 00:00:00
abstract::Sporulation in Saccharomyces cerevisiae normally occurs only in MATa/MAT alpha diploids. We show that mutations in RME1 bypassed the requirements for both a and alpha mating type information in sporulation and therefore allowed MATa/MATa and MAT alpha/MAT alpha diploids to sporulate. RME1 was located on chromosome VII...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.1.10.958
更新日期:1981-10-01 00:00:00
abstract::Intestinal alkaline phosphatase (IAP) is the most ancestral of the tissue-specific members of the AP gene family. Several studies have suggested an absorptive function for IAP, but in vivo data to this effect have been lacking. We inactivated the mouse IAP gene in embryo-derived stem cells and generated mice homozygou...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.21.7525-7530.2003
更新日期:2003-11-01 00:00:00