Abstract：
:An immature state of cellular differentiation--characterized by stem cell-like tendencies and impaired differentiation--is a hallmark of cancer. Using glioblastoma multiforme (GBM) as a model system, we sought to determine whether molecular determinants that drive cells toward terminal differentiation are also genetically targeted in carcinogenesis and whether neutralizing such genes also plays an active role to reinforce the impaired differentiation state and promote malignancy. To that end, we screened 71 genes with known roles in promoting nervous system development that also sustain copy number loss in GBM through antineoplastic assay and identified A2BP1 (ataxin 2 binding protein 1, Rbfox1), an RNA-binding and splicing regulator that is deleted in 10% of GBM cases. Integrated in silico analysis of GBM profiles to elucidate the A2BP1 pathway and its role in glioma identified myelin transcription factor 1-like (Myt1L) as a direct transcriptional regulator of A2BP1. Reintroduction of A2BP1 or Myt1L in GBM cell lines and glioma stem cells profoundly inhibited tumorigenesis in multiple assays, and conversely, shRNA-mediated knockdown of A2BP1 or Myt1L in premalignant neural stem cells compromised neuronal lineage differentiation and promoted orthotopic tumor formation. On the mechanistic level, with the top-represented downstream target TPM1 as an illustrative example, we demonstrated that, among its multiple functions, A2BP1 serves to regulate TPM1's alternative splicing to promote cytoskeletal organization and terminal differentiation and suppress malignancy. Thus, in addition to the activation of self-renewal pathways, the neutralization of genetic programs that drive cells toward terminal differentiation may also promote immature and highly plastic developmental states that contribute to the aggressive malignant properties of GBM.
journal_name
Proc Natl Acad Sci U S Aauthors
Hu J,Ho AL,Yuan L,Hu B,Hua S,Hwang SS,Zhang J,Hu T,Zheng H,Gan B,Wu G,Wang YA,Chin L,DePinho RAdoi
10.1073/pnas.1308610110subject
Has Abstractpub_date
2013-09-03 00:00:00pages
14520-7issue
36eissn
0027-8424issn
1091-6490pii
1308610110journal_volume
110pub_type
杂志文章abstract：:We prepared a stable cell line expressing the glucagon receptor to characterize the effect of G(s)-coupled receptor stimulation on extracellular signal-regulated protein kinase 1/2 (ERK1/2) activity. Glucagon treatment of the cell line caused a dose-dependent increase in cAMP concentration, activation of cAMP-dependen...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.131200398
更新日期：2001-08-28 00:00:00
abstract：:In rod photoreceptors, several phototransduction components display light-dependent translocation between cellular compartments. Notably, the G protein transducin translocates from rod outer segments to inner segments/spherules in bright light, but the functional consequences of translocation remain unclear. We genera...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1222666110
更新日期：2013-07-23 00:00:00
abstract：:The crown gall teratoma tumor line BT37, incited by Agrobacterium tumefaciens strain T37, has been found to contain part of the tumor-inducing plasmid, pTi T37, of the inciting strain. This foreign DNA segment, called T-DNA, is maintained at several copies per diploid tumor cell. We have examined subcellular DNA fract...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.77.7.4060
更新日期：1980-07-01 00:00:00
abstract：:Kinesin is the canonical plus-end microtubule motor and has been the focus of intense study since its discovery in 1985. We previously demonstrated a time-dependent inactivation of kinesin in vitro that was fully reversible by the addition of purified casein kinase 2 (CK2) and showed that this inactivation/reactivatio...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1321419111
更新日期：2014-05-13 00:00:00
abstract：:Glucocorticoids rapidly and completely inhibit intracellular plasminogen activator activity in rat hepatoma cells, as assayed by the solubilization of 125I-labeled fibrin. Experiments in which extracts of dexamethasone-treated cells are mixed with extracts of control cells demonstrate an inhibitor of protease activity...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.75.12.6130
更新日期：1978-12-01 00:00:00
abstract：:Retrotransposons and retroviruses integrate nonrandomly into eukaryotic genomes. For the yeast retrotransposon Ty5, integration preferentially occurs within domains of heterochromatin. Targeting to these locations is determined by interactions between an amino acid sequence motif at the C terminus of Ty5 integrase (IN...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1036705100
更新日期：2003-05-13 00:00:00
abstract：:Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish wheth...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0500178102
更新日期：2005-02-22 00:00:00
abstract：:Populations of isogenic embryonic stem cells or clonal bacteria often exhibit extensive phenotypic heterogeneity that arises from intrinsic stochastic dynamics of cells. The phenotypic state of a cell can be transmitted epigenetically in cell division, leading to correlations in the states of cells related by descent....
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1504407112
更新日期：2015-05-05 00:00:00
abstract：:We combine eight previously proposed measures to construct an index of political polarization among US adults. We find that polarization has increased the most among the demographic groups least likely to use the Internet and social media. Our overall index and all but one of the individual measures show greater incre...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1706588114
更新日期：2017-10-03 00:00:00
abstract：:Phosphoenolpyruvate carboxykinase (GTP) [GTP;oxaloacetate carboxy-lyase(transphosphorylating); EC 4.1.1.32] is absent in rat liver cytosol during fetal life and is synthesized initially at birth. De novo synthesis of the enzyme can be induced prematurely by injection of dibutyryl cyclic AMP or glucagon into fetal anim...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.75.9.4189
更新日期：1978-09-01 00:00:00
abstract：:Cytotactin is an extracellular matrix protein that is dynamically and transiently expressed in a place-dependent fashion during development by glial cells, fibroblasts, and several other cell types. In the present study, the effects of cytotactin on cell proliferation were examined in fibroblastic cells in culture. NI...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.88.24.11403
更新日期：1991-12-15 00:00:00
abstract：:The plant hormone abscisic acid (ABA) is produced in response to abiotic stresses and mediates stomatal closure in response to drought via recently identified ABA receptors (pyrabactin resistance/regulatory component of ABA receptor; PYR/RCAR). SLAC1 encodes a central guard cell S-type anion channel that mediates ABA-...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1116590109
更新日期：2012-06-26 00:00:00
abstract：:The Cdc28 protein kinase functions in the G1 to S phase transition of the cell cycle of the budding yeast Saccharomyces cerevisiae. This is in contrast with observations of the homologous protein kinase from a variety of metazoans, where activity and function are associated with the G2 to M phase transition. We presen...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.87.15.5697
更新日期：1990-08-01 00:00:00
abstract：:Despite the widespread occurrence of spliceosomal introns in the genomes of higher eukaryotes, their origin remains controversial. One model proposes that the duplication of small genomic portions could have provided the boundaries for new introns. If this mechanism has occurred recently, the 5' and 3' boundaries of e...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0604777104
更新日期：2007-01-16 00:00:00
abstract：:The role of anti-peripheral nerve myelin antibody (anti-PNM Ab) in the pathogenesis of acquired demyelination of peripheral nerve is unclear, in part, due to the poor correlation between antibody and disease activity. Previous studies show that only 27-50% of patients with acute demyelinating neuropathy or Guillain-Ba...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.82.3.905
更新日期：1985-02-01 00:00:00
abstract：:The presence of nerve growth factor (NGF) mRNA and protein in the rat central nervous system is documented. Blot-hybridization analysis showed an abundance of NGF mRNA in the hippocampus, cerebral cortex, and olfactory bulb. Enzyme immunoassay confirmed significant levels of a NGF-like protein in the hippocampus and c...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.83.3.817
更新日期：1986-02-01 00:00:00
abstract：:A screening procedure based on solvent extraction with minimal clean up followed by examination with negative chemical ionization mass spectrometry has been developed for organochlorine residues and related compounds with masses greater than 130 daltons. The procedure has been made quantitative for analysis of pentach...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.73.6.1777
更新日期：1976-06-01 00:00:00
abstract：:P-glycoprotein is an ATP-binding cassette multidrug transporter that actively transports chemically diverse substrates across the lipid bilayer. The precise molecular mechanism underlying transport is not fully understood. Here, we present crystal structures of a eukaryotic P-glycoprotein homolog, CmABCB1 from Cyanidi...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1321562111
更新日期：2014-03-18 00:00:00
abstract：:In the chalcone synthase gene of Antirrhinum majus (snapdragon), 150 base pairs of the 5' flanking region contain cis-acting signals for UV light-induced expression. A nuclear factor, designated CG-1, specifically recognizes a hexameric motif with internal dyad symmetry, CACGTG, located within this light-responsive se...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.86.18.6930
更新日期：1989-09-01 00:00:00
abstract：:We have recently established that several mRNAs encode the PR264/SC35 splicing factor and that their expression is related to that of c-Myb in human hematopoietic cells. We now report that the various PR264 mRNAs whose expression is transactivated by c-Myb proteins encode an identical PR264/SC35 polypeptide. These mRN...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.91.3.932
更新日期：1994-02-01 00:00:00
abstract：:Researchers have documented many cases in which individuals rationalize their regrettable actions. Four experiments examine situations in which people go beyond merely explaining away their misconduct to actively deceiving themselves. We find that those who exploit opportunities to cheat on tests are likely to engage ...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1010658108
更新日期：2011-09-13 00:00:00
abstract：:In yeasts and mammals, PEX10 encodes an integral membrane protein with a C3HC4 RING finger motif in its C-terminal domain and is required for peroxisome biogenesis and matrix protein import. In humans, its dysfunction in peroxisome biogenesis leads to severe Zellweger Syndrome and infantile Refsum disease. Here we sho...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1633697100
更新日期：2003-08-05 00:00:00
abstract：:Without a fully developed initial segment, the most proximal region of the epididymis, male infertility results. Therefore, it is important to understand the development and regulation of this crucial region. In addition to distinctively high activity levels of the components of the ERK pathway, which are essential fo...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1413186112
更新日期：2014-12-30 00:00:00
abstract：:The activated form of the third complement protein, C3b, forms a stable complex with components of plasma membranes and particulate entities such as zymosan. The complex resists the action of detergents and protein denaturants as well as extremes of temperature, salt concentration, and pH. It can, however, be broken b...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.74.7.2701
更新日期：1977-07-01 00:00:00
abstract：:Cell proliferation may be altered in many diseases, but it is uncertain exactly how to measure total numbers of divisions. Although it is impossible to count every division directly, potentially total numbers of stem cell divisions since birth may be inferred from numbers of somatic errors. The idea is that divisions ...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0503976102
更新日期：2005-12-06 00:00:00
abstract：:APOBEC3 (A3) genes are members of the AID/APOBEC gene family that are found exclusively in mammals. A3 genes encode antiviral proteins that restrict the replication of retroviruses by inducing G-to-A mutations in their genomes and have undergone extensive amplification and diversification during mammalian evolution. E...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1914183116
更新日期：2020-01-07 00:00:00
abstract：:Metagenomics is expanding our knowledge of the gene content, functional significance, and genetic variability in natural microbial communities. Still, there exists limited information concerning the regulation and dynamics of genes in the environment. We report here global analysis of expressed genes in a naturally oc...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.0708897105
更新日期：2008-03-11 00:00:00
abstract：:This work argues that, in a polarized environment, scientists can minimize the likelihood that the audience's biased processing will lead to rejection of their message if they not only eschew advocacy but also, convey that they are sharers of knowledge faithful to science's way of knowing and respectful of the audienc...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1320868111
更新日期：2014-09-16 00:00:00
abstract：:Innate immunity can facilitate nervous system regeneration, yet the underlying cellular and molecular mechanisms are not well understood. Here we show that intraocular injection of lipopolysaccharide (LPS), a bacterial cell wall component, or the fungal cell wall extract zymosan both lead to rapid and comparable intra...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1423221112
更新日期：2015-02-24 00:00:00
abstract：:Ride-sharing services are transforming urban mobility by providing timely and convenient transportation to anybody, anywhere, and anytime. These services present enormous potential for positive societal impacts with respect to pollution, energy consumption, congestion, etc. Current mathematical models, however, do not...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 杂志文章
doi：10.1073/pnas.1611675114
更新日期：2017-01-17 00:00:00
