Abstract:
:In the majority of human tumors, expression of the c-MYC oncogene becomes constitutive. Here, we report that c-MYC directly regulates the expression of AP4 via CACGTG motifs in the first intron of the AP4 gene. Induction of AP4 was required for c-MYC-mediated cell cycle reentry of anti-estrogen arrested breast cancer cells and mitogen-mediated repression of the CDK inhibitor p21. AP4 directly repressed p21 by occupying four CAGCTG motifs in the p21 promoter via its basic region. AP4 levels declined after DNA damage, and ectopic AP4 interfered with p53-mediated cell cycle arrest and sensitized cells to apoptosis induced by DNA damaging agents. AP4 expression blocked induction of p21 by TGF-beta in human keratinocytes and interfered with up-regulation of p21 and cell cycle arrest during monoblast differentiation. Notably, AP4 is specifically expressed in colonic progenitor and colorectal carcinoma cells. In conclusion, our results indicate that c-MYC employs AP4 to maintain cells in a proliferative, progenitor-like state.
journal_name
Proc Natl Acad Sci U S Aauthors
Jung P,Menssen A,Mayr D,Hermeking Hdoi
10.1073/pnas.0801773105subject
Has Abstractpub_date
2008-09-30 00:00:00pages
15046-51issue
39eissn
0027-8424issn
1091-6490pii
0801773105journal_volume
105pub_type
杂志文章abstract::We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. We accomplished this by conjugating the iron-transport protein transferrin to polycations that bind nucleic acids. Human transferrin, as well as the chicken homologue conalbu...
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.87.9.3410
更新日期:1990-05-01 00:00:00
abstract::Electron micrographs are shown of the first component of human complement (C1) which has been crosslinked with a water-soluble carbodiimide to prevent dissociation into its C1q and C1r2C1s2 subunits. Two projections of the crosslinked molecule are seen in the electron micrographs, which are called "top" and "profile."...
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.79.2.586
更新日期:1982-01-01 00:00:00
abstract::Actin filaments and integrin-based focal adhesions (FAs) form integrated systems that mediate dynamic cell interactions with their environment or other cells during migration, the immune response, and tissue morphogenesis. How adhesion-associated actin structures obtain their functional specificity is unclear. Here we...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,收录出版
doi:10.1073/pnas.1505035112
更新日期:2015-05-12 00:00:00
abstract::Bacterial RNases catalyze the turnover of RNA and are essential for gene expression and quality surveillance of transcripts. In Escherichia coli, the exoribonucleases RNase R and polynucleotide phosphorylase (PNPase) play critical roles in degrading RNA. Here, we developed an optical-trapping assay to monitor the tran...
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.1514028112
更新日期:2015-12-08 00:00:00
abstract::A subpopulation of phenobarbital-induced cytochrome P-450 in rat liver has been shown to consist of four closely related forms of the enzyme that appeared to be strain-related. In the present study, polypeptides composing this family were analyzed by two-dimensional electrophoresis of hepatic microsomes from 64 indivi...
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.80.21.6542
更新日期:1983-11-01 00:00:00
abstract::Copper is a required metal nutrient for life, but global or local alterations in its homeostasis are linked to diseases spanning genetic and metabolic disorders to cancer and neurodegeneration. Technologies that enable longitudinal in vivo monitoring of dynamic copper pools can help meet the need to study the complex ...
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.1613628113
更新日期:2016-12-13 00:00:00
abstract::Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably t...
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.1505315112
更新日期:2015-08-25 00:00:00
abstract::A genetic complementation system was developed in which tobacco etch virus (TEV) polymerase (NIb)-expressing transgenic plants or protoplasts were inoculated with NIb-defective TEV mutants. A beta-glucuronidase (GUS) reporter gene integrated into the genomes of parental and four mutant viruses was used to assay RNA am...
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.92.2.457
更新日期:1995-01-17 00:00:00
abstract::The localized maternal RNA Vg1 resides in the cortical region of the vegetal pole of fully grown Xenopus oocytes and is inherited by only a subset of blastomeres in the early embryo [Weeks, D. L. & Melton, D. A. (1987) Cell 51, 861-867]. Because RNA-cytoskeletal interactions may play a role in RNA localization, we hav...
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.85.20.7612
更新日期:1988-10-01 00:00:00
abstract::Stable isotope values of carbon (delta13C) and nitrogen (delta15N) in blood, feathers, eggshell, and bone have been used in seabird studies since the 1980s, providing a valuable source of information on diet, foraging patterns, and migratory behavior in these birds. These techniques can also be applied to fossil mater...
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.0608477104
更新日期:2007-07-10 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a ravaging condition of progressive lung scarring and destruction. Anti-inflammatory therapies including corticosteroids have limited efficacy in this ultimately fatal disorder. An important unmet need is to identify new agents that interact with key ...
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.1001520107
更新日期:2010-08-10 00:00:00
abstract::Inhomogeneous ab initio molecular dynamics simulations show that vaporization of MgSiO3 is incongruent and that the vapor phase is dominated by SiO and O2 molecules. The vapor is strongly depleted in Mg at low temperature and approaches the composition of the liquid near the critical point. We find that the liquid-vap...
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.1719134115
更新日期:2018-05-22 00:00:00
abstract::Fluorescence of quinacrine in the presence of different polynucleotides was studied to attempt to identify the specific nucleotides responsible for the fluorescence of stained chromosome preparations. A marked enhancement of fluorescence was seen in the presence of bihelical polynucleotides, such as poly(dA-dT), poly(...
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.69.3.629
更新日期:1972-03-01 00:00:00
abstract::The T-cell receptor (TCR) gamma gene product occurs in association with T3 (CD3) polypeptides on the surface of human T lymphocytes. TCR gamma lymphocytes express arrays of T3 polypeptides distinct from those typically observed on TCR alpha beta lymphocytes. This report demonstrates that identical T3 gamma, delta, and...
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.84.11.3817
更新日期:1987-06-01 00:00:00
abstract::Transient cytosolic Ca(2+) ([Ca(2+)](cyt)) elevations are early events in plant signaling pathways including those related to abiotic stress. The restoration of [Ca(2+)](cyt) to prestimulus levels involves ATP-driven Ca(2+) pumps, but direct evidence for an essential role of a plant Ca(2+)-ATPase in abiotic stress ada...
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.0800864105
更新日期:2008-12-09 00:00:00
abstract::For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effects on membrane excitabil...
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.1323541111
更新日期:2014-07-08 00:00:00
abstract::State transition in photosynthesis is a short-term balancing mechanism of energy distribution between photosystem I (PSI) and photosystem II (PSII). When PSII is preferentially excited (state 2), a pool of mobile light-harvesting complex II (LHCII) antenna proteins is thought to migrate from PSII to PSI, but biochemic...
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.0509952103
更新日期:2006-01-10 00:00:00
abstract::Banded iron formations (BIFs) record a time of extensive Fe deposition in the Precambrian oceans, but the sources and pathways for metals in BIFs remain controversial. Here, we present Fe- and Nd-isotope data that indicate two sources of Fe for the large BIF units deposited 2.5 billion y ago. High-εNd and -δ(56)Fe sig...
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.1505515112
更新日期:2015-07-07 00:00:00
abstract::Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of prima...
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.1404167111
更新日期:2015-01-13 00:00:00
abstract::CHD7 encodes an ATP-dependent chromatin remodeling factor. Mutation of this gene causes multiple developmental disorders, including CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth/development, Genital abnormalities, and Ear anomalies) syndrome, in which conotruncal anomalies a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2020-11-17 00:00:00
abstract::For disordered proteins, the dimensions of the chain are an important property that is sensitive to environmental conditions. We have used single-molecule Förster resonance energy transfer to probe the temperature-induced chain collapse of five unfolded or intrinsically disordered proteins. Because this behavior is 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.1313006111
更新日期:2014-04-08 00:00:00
abstract::The thyroid hormone and retinoid X receptors form a heterodimer with each other and mediate thyroid hormone (T3)-dependent transcription. Retinoid X receptor, in addition, forms a homodimer and mediates 9-cis-retinoic acid-dependent transcription. Here, recombinant thyroid hormone receptor and recombinant retinoid X r...
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.91.5.1647
更新日期:1994-03-01 00:00:00
abstract::Stearoyl-CoA desaturase (SCD) is a key regulator of membrane fluidity, turns over rapidly, and represents a model for selective degradation of short-lived proteins of the endoplasmic reticulum (ER). The mechanism whereby specific ER proteins are targeted for degradation in the midst of stable proteins coexisting in th...
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.97.16.8883
更新日期:2000-08-01 00:00:00
abstract::Conformationally compromised oncogenic mutants of the tumor suppressor protein p53 can, in principle, be rescued by small molecules that bind the native, but not the denatured state. We describe a strategy for the rational search for such molecules. A nine-residue peptide, CDB3, which was derived from a p53 binding pr...
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.241629998
更新日期:2002-01-22 00:00:00
abstract::Breast cancers show variable sensitivity to paclitaxel. There is no diagnostic test to identify tumors that are sensitive to this drug. We used U133A chips to identify genes that are associated with pathologic complete response (pCR) to preoperative paclitaxel-containing chemotherapy in stage I-III breast cancer (n = ...
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.0408974102
更新日期:2005-06-07 00:00:00
abstract::The Rev protein of HIV-1, which facilitates the nuclear export of HIV-1 pre-mRNAs, has been a target for antiviral therapy. Here we describe a new strategy for inhibiting Rev function and HIV-1 replication. In contrast to previous approaches, we use a wild-type rather than a mutant Rev protein and covalently link this...
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.93.17.8873
更新日期:1996-08-20 00:00:00
abstract::The free radicals nitric oxide and superoxide anion react to form peroxynitrite (ONOO-), a highly toxic oxidant species. In vivo formation of ONOO- has been demonstrated in shock and inflammation. Herein we provide evidence that cytotoxicity in cells exposed to ONOO- is mediated by DNA strand breakage and the subseque...
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.93.5.1753
更新日期:1996-03-05 00:00:00
abstract::Transgenic mice have provided invaluable information about gene function and regulation. However, because of marked differences between rodents and primates, some areas of human biology such as early embryonic development, aging, and maternal-fetal interactions would be best studied in a nonhuman primate model. Here, ...
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.181336098
更新日期:2001-09-11 00:00:00
abstract::We have examined whether dissociation of the histone octamer is required for elongation of RNA transcripts through arrays of nucleosome cores in vitro. Control or dimethyl suberimidate-crosslinked histone octamers were reconstituted onto supercoiled, closed circular pT207-18 DNA, which contains tandemly repeated 207-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.90.13.6203
更新日期:1993-07-01 00:00:00
abstract::We prove that the property of excision in algebraic K-theory is for a Q-algebra A equivalent to the H-unitality of the latter. Our excision theorem, in particular, implies Karoubi's conjecture on the equality of algebraic and topological K-theory groups of stable C*-algebras. It also allows us to identify the algebrai...
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.87.24.9582
更新日期:1990-12-15 00:00:00