Nuclear PTEN-mediated growth suppression is independent of Akt down-regulation.

Abstract:

:The tumor suppressor gene PTEN is a phosphoinositide phosphatase that is inactivated by deletion and/or mutation in diverse human tumors. Wild-type PTEN is expressed both in the cytoplasm and nucleus in normal cells, with a preferential nuclear localization in differentiated or resting cells. To elucidate the relationship between PTEN's subcellular localization and its biologic activities, we constructed different PTEN mutants that targeted PTEN protein into different subcellular compartments. Our data show that the subcellular localization patterns of a PTEN (deltaPDZB) mutant versus a G129R phosphatase mutant were indistinguishable from those of wild-type PTEN. In contrast, the Myr-PTEN mutant demonstrated an enhanced association with the cell membrane. We found that nuclear PTEN alone is capable of suppressing anchorage-independent growth and facilitating G1 arrest in U251MG cells without inhibiting Akt activity. Nuclear compartment-specific PTEN-induced growth suppression is dependent on possessing a functional lipid phosphatase domain. In addition, the down-regulation of p70S6K could be mediated, at least in part, through activation of AMP-activated protein kinase in an Akt-independent fashion. Introduction of a constitutively active mutant of Akt, Akt-DD, only partially rescues nuclear PTEN-mediated growth suppression. Our collective results provide the first direct evidence that PTEN can contribute to G1 growth arrest through an Akt-independent signaling pathway.

journal_name

Mol Cell Biol

authors

Liu JL,Sheng X,Hortobagyi ZK,Mao Z,Gallick GE,Yung WK

doi

10.1128/MCB.25.14.6211-6224.2005

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

6211-24

issue

14

eissn

0270-7306

issn

1098-5549

pii

25/14/6211

journal_volume

25

pub_type

杂志文章
  • De Novo RNA Synthesis by RNA-Dependent RNA Polymerase Activity of Telomerase Reverse Transcriptase.

    abstract::RNA-dependent RNA polymerase (RdRP) plays key roles in RNA silencing to generate double-stranded RNAs. In model organisms, such as Caenorhabditis elegans and Neurospora crassa, two types of small interfering RNAs (siRNAs), primary siRNAs and secondary siRNAs, are expressed; RdRP produces secondary siRNAs de novo, with...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01021-15

    authors: Maida Y,Yasukawa M,Masutomi K

    更新日期:2016-03-31 00:00:00

  • Unusual enhancer function in yeast rRNA transcription.

    abstract::The rRNA genes in most eucaryotic organisms are present in a tandem array. There is substantial evidence that transcription of one of these genes may not be independent of transcription of others. In particular, in the yeast Saccharomyces cerevisiae, the enhancer of rRNA transcription that lies 2.2 kilobases 5' of the...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.11.4986

    authors: Johnson SP,Warner JR

    更新日期:1989-11-01 00:00:00

  • Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease.

    abstract::The epidermal growth factor (EGF) receptor is the functional target of the mitogen EGF and the cellular homolog of the avian erythroblastosis virus erbB oncogene product. Regulation of expression of the proto-oncogene encoding the EGF receptor can be elucidated by studying the structure and function of the gene promot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.10.4174

    authors: Johnson AC,Jinno Y,Merlino GT

    更新日期:1988-10-01 00:00:00

  • Double-stranded RNA-binding protein regulates vascular endothelial growth factor mRNA stability, translation, and breast cancer angiogenesis.

    abstract::Vascular endothelial growth factor (VEGF) is a key angiogenic factor expressed under restricted nutrient and oxygen conditions in most solid tumors. The expression of VEGF under hypoxic conditions requires transcription through activated hypoxia-inducible factor 1 (HIF-1), increased mRNA stability, and facilitated tra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.02078-06

    authors: Vumbaca F,Phoenix KN,Rodriguez-Pinto D,Han DK,Claffey KP

    更新日期:2008-01-01 00:00:00

  • Domain structure of the simian virus 40 core origin of replication.

    abstract::The simian virus 40 core origin of replication consists of nucleotides 5211 through 31. These 64 base pairs contain three functional domains with strict sequence requirements and two spacer regions with relaxed sequence specificity but precise positional constraints. The early domain extends for 10 contiguous base pai...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.5.1663

    authors: Deb S,DeLucia AL,Baur CP,Koff A,Tegtmeyer P

    更新日期:1986-05-01 00:00:00

  • The peroxin Pex17p of the yeast Yarrowia lipolytica is associated peripherally with the peroxisomal membrane and is required for the import of a subset of matrix proteins.

    abstract::PEX genes encode peroxins, which are required for the biogenesis of peroxisomes. The Yarrowia lipolytica PEX17 gene encodes the peroxin Pex17p, which is 671 amino acids in length and has a predicted molecular mass of 75,588 Da. Pex17p is peripherally associated with the peroxisomal membrane. The carboxyl-terminal trip...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.5.2511

    authors: Smith JJ,Szilard RK,Marelli M,Rachubinski RA

    更新日期:1997-05-01 00:00:00

  • Identification of a signal for nuclear targeting in platelet-derived-growth-factor-related molecules.

    abstract::The v-vis gene encodes p28sis, the transforming protein of simian sarcoma virus. This gene resulted from a fusion of the env gene of simian sarcoma-associated virus and the woolly monkey gene for the B chain of platelet-derived growth factor (PDGF). Previous work has shown that the v-sis gene product undergoes signal ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.10.3527

    authors: Lee BA,Maher DW,Hannink M,Donoghue DJ

    更新日期:1987-10-01 00:00:00

  • Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae.

    abstract::Ribonucleotide reductase (RNR), which catalyzes the rate-limiting step for deoxyribonucleotide production required for DNA synthesis, is an alpha2beta2 tetramer consisting of two large and two small subunits. RNR2 encodes a small subunit and is essential for mitotic viability in Saccharomyces cerevisiae. We have clone...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.10.6105

    authors: Huang M,Elledge SJ

    更新日期:1997-10-01 00:00:00

  • Expression of the three human major histocompatibility complex class II isotypes exhibits a differential dependence on the transcription factor RFXAP.

    abstract::Major histocompatibility complex class II (MHCII) molecules play a pivotal role in the immune system because they direct the development and activation of CD4(+) T cells. There are three human MHCII isotypes, HLA-DR, HLA-DQ, and HLA-DP. Key transcription factors controlling MHCII genes have been identified by virtue o...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.21.17.5699-5709.2001

    authors: Peretti M,Villard J,Barras E,Zufferey M,Reith W

    更新日期:2001-09-01 00:00:00

  • cis-acting regulatory elements within gag genes of avian retroviruses.

    abstract::A cis-acting enhancer element has been detected within the gag gene of several avian retroviruses, including Rous sarcoma virus, Fujinami sarcoma virus, and the endogenous Rous-associated virus-0. A consensus enhancer core sequence, GTGGTTTG, is present in all of these viral genomes, approximately 900 bases downstream...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.1.388

    authors: Arrigo S,Yun M,Beemon K

    更新日期:1987-01-01 00:00:00

  • The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase.

    abstract::Transposons have contributed protein coding sequences to a unexpectedly large number of human genes. Except for the V(D)J recombinase and telomerase, all remain of unknown function. Here we investigate the activity of the human SETMAR protein, a highly expressed fusion between a histone H3 methylase and a mariner fami...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01899-06

    authors: Liu D,Bischerour J,Siddique A,Buisine N,Bigot Y,Chalmers R

    更新日期:2007-02-01 00:00:00

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

    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

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

    更新日期:2009-01-01 00:00:00

  • Developmental and cell type specificity of LINE-1 expression in mouse testis: implications for transposition.

    abstract::The LINE-1, or L1, family of interspersed repeated DNA constitutes roughly 10% of the mammalian genome. Its abundance is due to duplicative transposition via an RNA intermediate, L1-encoded proteins, and reverse transcription. Although, in principle, transposition may occur in any cell type, expression and transpositi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.4.2584

    authors: Branciforte D,Martin SL

    更新日期:1994-04-01 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

  • Stability of a human SWI-SNF remodeled nucleosomal array.

    abstract::SWI-SNF alters DNA-histone interactions within a nucleosome in an ATP-dependent manner. These alterations cause changes in the topology of a closed circular nucleosomal array that persist after removal of ATP from the reaction. We demonstrate here that a remodeled closed circular array will revert toward its original ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.4.1132-1144.2001

    authors: Guyon JR,Narlikar GJ,Sullivan EK,Kingston RE

    更新日期:2001-02-01 00:00:00

  • The immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription.

    abstract::We demonstrate that the immunoglobulin heavy-chain enhancer functions as the promoter for I mu sterile transcription. The enhancer itself, when placed 5' to the bacterial cat or neo genes, is able to direct transcription by using heterogeneous start sites that are generally the same as those found with bona fide I mu ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.2619

    authors: Su LK,Kadesch T

    更新日期:1990-06-01 00:00:00

  • Stimulation of cell proliferation by endosomal epidermal growth factor receptor as revealed through two distinct phases of signaling.

    abstract::Strong evidence indicates that endosome-localized epidermal growth factor receptor (EGFR) plays an important role in cell signaling. However, elimination of endosomal signaling does not attenuate EGF-induced physiological outcomes, arguing against physiological relevance. Recently we established a system to specifical...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.16.5803-5815.2003

    authors: Pennock S,Wang Z

    更新日期:2003-08-01 00:00:00

  • Rad53 checkpoint kinase phosphorylation site preference identified in the Swi6 protein of Saccharomyces cerevisiae.

    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

    authors: Sidorova JM,Breeden LL

    更新日期:2003-05-01 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

  • Dissection of Ras-dependent signaling pathways controlling aggressive tumor growth of human fibrosarcoma cells: evidence for a potential novel pathway.

    abstract::Activation of multiple signaling pathways is required to trigger the full spectrum of in vitro and in vivo phenotypic traits associated with neoplastic transformation by oncogenic Ras. To determine which of these pathways are important for N-ras tumorigenesis in human cancer cells and also to investigate the possibili...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.24.9294-9306.2000

    authors: Gupta S,Plattner R,Der CJ,Stanbridge EJ

    更新日期:2000-12-01 00:00:00

  • The requirement of heat shock cognate 70 protein for mitochondrial import varies among precursor proteins and depends on precursor length.

    abstract::The cytosolic heat shock cognate 70-kDa protein (hsc70) is required for efficient import of ornithine transcarbamylase precursor (pOTC) into rat liver mitochondria (K. Terada, K. Ohtsuka, N. Imamoto, Y. Yoneda, and M. Mori, Mol. Cell. Biol. 15:3708-3713, 1995). The requirement of hsc70 for mitochondrial import of vari...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.11.6103

    authors: Terada K,Ueda I,Ohtsuka K,Oda T,Ichiyama A,Mori M

    更新日期:1996-11-01 00:00:00

  • Osteogenesis Is Improved by Low Tumor Necrosis Factor Alpha Concentration through the Modulation of Gs-Coupled Receptor Signals.

    abstract::In the early phase of bone damage, low concentrations of the cytokine tumor necrosis factor alpha (TNF-α) favor osteoblast differentiation. In contrast, chronic high doses of the same cytokine contribute to bone loss, demonstrating opposite effects depending on its concentration and on the time of exposure. In the bon...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00442-16

    authors: Daniele S,Natali L,Giacomelli C,Campiglia P,Novellino E,Martini C,Trincavelli ML

    更新日期:2017-03-31 00:00:00

  • Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex.

    abstract::The gene encoding the SNF5/Ini1 core subunit of the SWI/SNF chromatin remodeling complex is a tumor suppressor in humans and mice, with an essential role in early embryonic development. To investigate further the function of this gene, we have generated a Cre/lox-conditional mouse line. We demonstrate that Snf5 deleti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.7.2661-2674.2006

    authors: Klochendler-Yeivin A,Picarsky E,Yaniv M

    更新日期:2006-04-01 00:00:00

  • The nuclear import of TAF10 is regulated by one of its three histone fold domain-containing interaction partners.

    abstract::TFIID, comprising the TATA box binding protein (TBP) and 13 TBP-associated factors (TAFs), plays a role in nucleation in the assembly of the RNA polymerase II preinitiation complexes on protein-encoding genes. TAFs are shared among other transcription regulatory complexes (e.g., SAGA, TBP-free TAF-containing complex [...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.10.4092-4104.2005

    authors: Soutoglou E,Demény MA,Scheer E,Fienga G,Sassone-Corsi P,Tora L

    更新日期:2005-05-01 00:00:00

  • SWI-SNF-mediated nucleosome remodeling: role of histone octamer mobility in the persistence of the remodeled state.

    abstract::SWI-SNF is an ATP-dependent chromatin remodeling complex that disrupts DNA-histone interactions. Several studies of SWI-SNF activity on mononucleosome substrates have suggested that remodeling leads to novel, accessible nucleosomes which persist in the absence of continuous ATP hydrolysis. In contrast, we have reporte...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.9.3058-3068.2000

    authors: Jaskelioff M,Gavin IM,Peterson CL,Logie C

    更新日期:2000-05-01 00:00:00

  • Transcriptional activity of neural retina leucine zipper (Nrl) is regulated by c-Jun N-terminal kinase and Tip60 during retina development.

    abstract::Neural retina leucine zipper (Nrl), a key basic motif leucine zipper (bZIP) transcription factor, modulates rod photoreceptor differentiation by activating rod-specific target genes. In searching for factors that might couple with Nrl to modulate its transcriptional activity through posttranslational modification, we ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06440-11

    authors: Kim JW,Jang SM,Kim CH,An JH,Choi KH

    更新日期:2012-05-01 00:00:00

  • Nucleotide sequences required for the regulation of a rat alpha 2u-globulin gene by glucocorticoids.

    abstract::alpha 2u-Globulin is a rat protein of as yet unknown function whose synthesis can be induced by glucocorticoids and several other hormones. Induction by glucocorticoids is a secondary response to the hormone: protein synthesis is required before the hormone can exert its stimulatory effect on alpha 2u-globulin transcr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.7.2334

    authors: Addison WR,Kurtz DT

    更新日期:1986-07-01 00:00:00

  • Differential interactions of specific nuclear factor I isoforms with the glucocorticoid receptor and STAT5 in the cooperative regulation of WAP gene transcription.

    abstract::The distal region (-830 to -720 bp) of the rat whey acidic protein (WAP) gene contains a composite response element (CoRE), which has been demonstrated previously to confer mammary gland-specific and hormonally regulated WAP gene expression. Point mutations in the binding sites for specific transcription factors prese...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.20.6859-6869.2001

    authors: Mukhopadhyay SS,Wyszomierski SL,Gronostajski RM,Rosen JM

    更新日期:2001-10-01 00:00:00

  • Positive selection of FLP-mediated unequal sister chromatid exchange products in mammalian cells.

    abstract::Site-specific recombination provides a powerful tool for studying gene function at predetermined chromosomal sites. Here we describe the use of a blasticidin resistance system to select for recombination in mammalian cells using the yeast enzyme FLP. The vector is designed so that site-specific recombination reconstru...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.2.857

    authors: Aladjem MI,Brody LL,O'Gorman S,Wahl GM

    更新日期:1997-02-01 00:00:00

  • Transcription factor binding is limited by the 5'-flanking regions of a Drosophila tRNAHis gene and a tRNAHis pseudogene.

    abstract::We determined the sequence of a Drosophila tRNA gene cluster containing a tRNAHis gene and a tRNAHis pseudogene in close proximity on the same DNA strand. The pseudogene contains eight consecutive base pairs different from the region of the bona fide gene which codes for the 3' portion of the anticodon stem of tRNAHis...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.12.2714

    authors: Cooley L,Schaack J,Burke DJ,Thomas B,Söll D

    更新日期:1984-12-01 00:00:00