Abstract:
:Oncogene-induced senescence (OIS) is a critical tumor-suppressing mechanism that restrains cancer progression at premalignant stages, in part by causing telomere dysfunction. Currently it is unknown whether this proliferative arrest presents a stable and therefore irreversible barrier to cancer progression. Here we demonstrate that cells frequently escape OIS induced by oncogenic H-Ras and B-Raf, after a prolonged period in the senescence arrested state. Cells that had escaped senescence displayed high oncogene expression levels, retained functional DNA damage responses, and acquired chromatin changes that promoted c-Myc-dependent expression of the human telomerase reverse transcriptase gene (hTERT). Telomerase was able to resolve existing telomeric DNA damage response foci and suppressed formation of new ones that were generated as a consequence of DNA replication stress and oncogenic signals. Inhibition of MAP kinase signaling, suppressing c-Myc expression, or inhibiting telomerase activity, caused telomere dysfunction and proliferative defects in cells that had escaped senescence, whereas ectopic expression of hTERT facilitated OIS escape. In human early neoplastic skin and breast tissue, hTERT expression was detected in cells that displayed features of senescence, suggesting that reactivation of telomerase expression in senescent cells is an early event during cancer progression in humans. Together, our data demonstrate that cells arrested in OIS retain the potential to escape senescence by mechanisms that involve derepression of hTERT expression.
journal_name
Proc Natl Acad Sci U S Aauthors
Patel PL,Suram A,Mirani N,Bischof O,Herbig Udoi
10.1073/pnas.1602379113subject
Has Abstractpub_date
2016-08-23 00:00:00pages
E5024-33issue
34eissn
0027-8424issn
1091-6490pii
1602379113journal_volume
113pub_type
杂志文章abstract::Mosquitoes transmit devastating human diseases because they need vertebrate blood for egg development. Metabolism in female mosquitoes is tightly coupled with blood meal-mediated reproduction, which requires an extremely high level of energy consumption. Functional analysis has shown that major genes encoding for enzy...
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.1619326114
更新日期:2017-03-28 00:00:00
abstract::To understand the evolution of a Theory of Mind, we need to understand the selective factors that might have jumpstarted its initial evolution. We argue that a subconscious, reflexive appreciation of others' intentions, emotions, and perspectives is at the roots of even the most complex forms of Theory of Mind and tha...
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.1301223110
更新日期:2013-06-18 00:00:00
abstract::Cytochrome c oxidase (ferrocytochrome c: oxygen oxidoreductase, EC 1.9.3.1) has been resolved into a pair of complexes of unequal molecular weight. The larger complex (electron transfer complex) contains exclusively the oxidation-reduction proteins characteristic of cytochrome oxidase; the smaller complex (ion transfe...
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.75.12.5908
更新日期:1978-12-01 00:00:00
abstract::The role played by postsynaptic alpha-adrenergic receptors in the stimulation of pineal N-acetyltransferase (EC 2.3.1.5) and [3H]melatonin production was investigated in the rat. In vivo studies indicated that phenylephrine, an alpha-adrenergic agonist, potentiated and prolonged the effects of isoproterenol, a beta-ad...
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.80.2.599
更新日期:1983-01-01 00:00:00
abstract::The discovery of a steadily growing number of tumor antigens (TAs) has made generic, cell-free, peptide-based cancer vaccines a possible alternative to cytokine-transfected autologous cellular cancer vaccines. The major drawback of peptide vaccines, however, is the poor immunogenicity of peptides. It is commonly thoug...
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.94.7.3256
更新日期:1997-04-01 00:00:00
abstract::The fungus, Phycomyces blakesleeanus, shows many well-defined responses to a number of external stimuli. Genetic analysis shows that at least eight genes are involved in Phycomyces sensory transduction. As a first step toward the molecular analysis of these genes and their products, we have developed a transformation ...
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.83.19.7344
更新日期:1986-10-01 00:00:00
abstract::A cDNA clone encoding the mRNA for the highly polymorphic human enzyme phosphoglucomutase 1 (PGM1; EC 5.4.2.2) has been isolated and characterized. This was achieved indirectly by first isolating a rabbit cDNA from an expression library using anti-rabbit PGM antibodies. A comparison of the nucleotide sequences shows 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.89.1.411
更新日期:1992-01-01 00:00:00
abstract::Peanut or groundnut (Arachis hypogaea L.), a legume of South American origin, has high seed oil content (45-56%) and is a staple crop in semiarid tropical and subtropical regions, partially because of drought tolerance conferred by its geocarpic reproductive strategy. We present a draft genome of the peanut A-genome p...
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.1600899113
更新日期:2016-06-14 00:00:00
abstract::Neurobiological theories of awareness propose divergent accounts of the spatial extent of brain changes that support conscious perception. Whereas focal theories posit mostly local regional changes, global theories propose that awareness emerges from the propagation of neural signals across a broad extent of sensory a...
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.1414466112
更新日期:2015-03-24 00:00:00
abstract::Nonribosomal peptides and polyketides are a diverse group of natural products with complex chemical structures and enormous pharmaceutical potential. They are synthesized on modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzyme complexes by a conserved thiotemplate mechanism. Here, we rep...
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.1401734111
更新日期:2014-06-24 00:00:00
abstract::These experiments investigate the capacity of thalamic and cortical structures in a sensory system to process information of a modality normally associated with another system. Retinal ganglion cells in newborn Syrian hamsters were made to project permanently to the main thalamic somatosensory (ventrobasal) nucleus. W...
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.86.1.357
更新日期:1989-01-01 00:00:00
abstract::Using a genome-wide approach, we asked how many transporter genes contribute to symbiotic phosphate uptake and analyzed their evolutionary conservation. Considering the sequenced rice genome at hand, only the Oryza sativa phosphate transporter (OsPT) gene OsPT11 was specifically induced during the arbuscular mycorrhiz...
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.202474599
更新日期:2002-10-01 00:00:00
abstract::A potential human footprint on Western Central African rainforests before the Common Era has become the focus of an ongoing controversy. Between 3,000 y ago and 2,000 y ago, regional pollen sequences indicate a replacement of mature rainforests by a forest-savannah mosaic including pioneer trees. Although some studies...
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.1715336115
更新日期:2018-03-27 00:00:00
abstract::We have developed a reliable genetic selection strategy for isolating interacting proteins based on the "hitchhiker" mechanism of the Escherichia coli twin-arginine translocation (Tat) pathway. This method, designated FLI-TRAP (functional ligand-binding identification by Tat-based recognition of associating proteins),...
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.0704048106
更新日期:2009-03-10 00:00:00
abstract::The adzuki bean beetle, Callosobruchus chinensis, is triple-infected with distinct lineages of Wolbachia endosymbiont, wBruCon, wBruOri, and wBruAus, which were identified by their wsp (Wolbachia surface protein) gene sequences. Whereas wBruCon and wBruOri caused cytoplasmic incompatibility of the host insect, wBruAus...
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.222228199
更新日期:2002-10-29 00:00:00
abstract::Apomixis is a naturally occurring mode of reproduction that results in embryo formation without the involvement of meiosis or fertilization of the egg. Seed-derived progeny of an apomictic plant are genetically identical to the maternal parent. We are studying a form of apomixis called apospory that occurs in the genu...
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.95.9.5127
更新日期:1998-04-28 00:00:00
abstract::Biotin plays an essential role in growth of mycobacteria. Synthesis of the cofactor is essential for Mycobacterium tuberculosis to establish and maintain chronic infections in a murine model of tuberculosis. Although the late steps of mycobacterial biotin synthesis, assembly of the heterocyclic rings, are thought to f...
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.2010189117
更新日期:2020-09-22 00:00:00
abstract::In isogamous species of Chlamydomonas, such as Chlamydomonas reinhardtii and Chlamydomonas eugametos, the sexual process involves the use of flagella agglutinins by which the gametes of compatible strains adhere through chance encounter and ultimately pair and fuse to form zygotes. In a newly described heterogamous sp...
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.92.2.641
更新日期:1995-01-17 00:00:00
abstract::The isolated beta subunit of hemoglobin Kansas has an oxygen affinity that is as low relative to the oxygen affinity of the beta(A) subunit as the affinity of hemoglobin Kansas is low relative to hemoglobin A. Thus the low affinity properties of hemoglobin Kansas are almost completely reflected in the properties of 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.70.6.1718
更新日期:1973-06-01 00:00:00
abstract::Complement receptors (CRs), expressed notably on myeloid and lymphoid cells, play an essential function in the elimination of complement-opsonized pathogens and apoptotic/necrotic cells. In addition, these receptors are crucial for the cross-talk between the innate and adaptive branches of the immune system. CR3 (also...
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.1311261110
更新日期:2013-10-08 00:00:00
abstract::Land plants have distinct developmental programs in haploid (gametophyte) and diploid (sporophyte) generations. Although usually the two programs strictly alternate at fertilization and meiosis, one program can be induced during the other program. In a process called apogamy, cells of the gametophyte other than the eg...
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.0906997106
更新日期:2009-09-22 00:00:00
abstract::Young male baboons born in captivity were immunized with an attenuated, cryopreserved schistosomular vaccine derived from gamma-irradiated (50 krad) cercariae of the Puerto Rican strain of Schistosoma mansoni. Protection against a heterologous Kenyan strain of S. mansoni, after percutaneous infection, was assessed. Pa...
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.81.11.3552
更新日期:1984-06-01 00:00:00
abstract::Breast tumors lacking expression of human epidermal growth factor receptor 2 (HER2) and the estrogen and the progesterone receptors (triple negative; TNBC) are more aggressive than other disease subtypes, and no molecular targeted agents are currently available for their treatment. Because TNBC commonly displays EGF 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.1220763110
更新日期:2013-01-29 00:00:00
abstract::RNA-dependent RNA polymerases (RdRps) of the Nidovirales (Coronaviridae, Arteriviridae, and 12 other families) are linked to an amino-terminal (N-terminal) domain, called NiRAN, in a nonstructural protein (nsp) that is released from polyprotein 1ab by the viral main protease (Mpro). Previously, self-GMPylation/UMPylat...
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.2022310118
更新日期:2021-02-09 00:00:00
abstract::The cytokine IFN-γ is a critical regulator of immune system development and function. Almost all leukocytes express the receptor for IFN-γ, yet each cell type elicits a different response to this cytokine. Cell type-specific effects of IFN-γ make it difficult to predict the outcomes of the systemic IFN-γ blockade 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.1804556115
更新日期:2018-11-06 00:00:00
abstract::Thymidine dinucleotide (pTpT) stimulates melanogenesis in mammalian pigment cells and intact skin, mimicking the effects of UV irradiation and UV-mimetic DNA damage. Here it is shown that, in addition to tanning, pTpT induces a second photoprotective response, enhanced repair of UV-induced DNA damage. This enhanced re...
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.94.23.12627
更新日期:1997-11-11 00:00:00
abstract::The phosphorylation of H2Ax on its S139 site, γH2Ax, is important during DNA double-strand repair and is considered necessary for assembly of repair complexes, but its functional role after other kinds of DNA damage is less clear. We have measured the survival of isogenic mouse cell lines with the H2Ax gene knocked ou...
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.1105866108
更新日期:2011-05-24 00:00:00
abstract::The MHC class I antigen presentation pathway allows the immune system to distinguish between self and nonself. Despite extensive research on the processing of antigenic peptides, little is known about their origin. Here, we show that mRNAs carrying premature stop codons that prevent the production of full-length prote...
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.1104104108
更新日期:2011-07-12 00:00:00
abstract::Antigen.antibody complexes (Ag.Ab) prepared from (125)I-labeled bovine serum albumin and guinea pig anti-albumin were incubated at 37 degrees C for 30 min with normal human serum diluted optimally for binding (1:16) and then with autologous erythrocytes (RBC). After washing, RBC-bearing antigen.antibody.complement com...
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.79.16.5047
更新日期:1982-08-01 00:00:00
abstract::In spite of the critical role of the process of adaptation in evolution, there are few detailed studies of the genotypic and molecular basis of the process. Drosophila melanogaster flies selected for increased tolerance to ethanol exhibited higher levels of alcohol dehydrogenase (alcohol:NAD+ oxidoreductase; EC 1.1.1....
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.74.10.4562
更新日期:1977-10-01 00:00:00