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 Bioljournal_title
Molecular and cellular biologyauthors
Liu JL,Sheng X,Hortobagyi ZK,Mao Z,Gallick GE,Yung WKdoi
10.1128/MCB.25.14.6211-6224.2005subject
Has Abstractpub_date
2005-07-01 00:00:00pages
6211-24issue
14eissn
0270-7306issn
1098-5549pii
25/14/6211journal_volume
25pub_type
杂志文章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
更新日期:2016-03-31 00:00:00
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
更新日期:1989-11-01 00:00:00
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
更新日期:1988-10-01 00:00:00
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
更新日期:2008-01-01 00:00:00
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
更新日期:1986-05-01 00:00:00
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
更新日期:1997-05-01 00:00:00
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
更新日期:1987-10-01 00:00:00
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
更新日期:1997-10-01 00:00:00
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
更新日期:2001-09-01 00:00:00
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
更新日期:1987-01-01 00:00:00
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
更新日期:2007-02-01 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::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
更新日期:1994-04-01 00:00:00
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
更新日期:1988-09-01 00:00:00
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
更新日期:2001-02-01 00:00:00
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
更新日期:1990-06-01 00:00:00
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
更新日期:2003-08-01 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 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
更新日期:1996-12-01 00:00:00
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
更新日期:2000-12-01 00:00:00
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
更新日期:1996-11-01 00:00:00
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
更新日期:2017-03-31 00:00:00
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
更新日期:2006-04-01 00:00:00
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
更新日期:2005-05-01 00:00:00
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
更新日期:2000-05-01 00:00:00
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
更新日期:2012-05-01 00:00:00
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
更新日期:1986-07-01 00:00:00
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
更新日期:2001-10-01 00:00:00
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
更新日期:1997-02-01 00:00:00
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
更新日期:1984-12-01 00:00:00