Abstract:
:Resistance to ionizing radiation (IR), which is a conventional treatment for osteosarcoma that cannot be resected, undermines the efficacy of this therapy. However, the mechanism by which IR induces radioresistance in osteosarcoma is not defined. Here, we report that CR6-interacting factor-1 (CRIF1) is highly expressed in osteosarcoma and undergoes nuclear-cytoplasmic shuttling of cyclin-dependent kinase 2 (CDK2) after IR. Osteosarcoma cells lacking CRIF1 show increased sensitivity to IR, which is associated with delayed DNA damage repair, inactivated G1/S checkpoint, and mitochondrial dysfunction. CRIF1 interacts with the DNA damage checkpoint regulator CDK2, and CRIF1 and CDK2 colocalize in the nucleus after IR. Nuclear localization of CDK2 is associated with phosphorylation changes that promote DNA repair and activation of the G1/S checkpoint. CRIF1 knockdown synergized with IR in an in vivo osteosarcoma model, leading to tumor regression. Based on these findings, we identify CRIF1 as a potential therapeutic target in osteosarcoma that can increase the efficacy of radiotherapy. More broadly, our findings may provide insights into the mechanism for other types of radioresistant cancers and be exploited for therapeutic ends.
journal_name
Proc Natl Acad Sci U S Aauthors
Ran Q,Jin F,Xiang Y,Xiang L,Wang Q,Li F,Chen L,Zhang Y,Wu C,Zhou L,Xiao Y,Chen L,Wu J,Zhong JF,Li SC,Li Zdoi
10.1073/pnas.1906578116subject
Has Abstractpub_date
2019-10-08 00:00:00pages
20511-20516issue
41eissn
0027-8424issn
1091-6490pii
1906578116journal_volume
116pub_type
杂志文章abstract::Creatine kinase (CK; EC 2.7.3.2) plays an important role in energy metabolism in brain and muscle. Expression of CK isoenzymes is regulated during development and is tissue specific. To define the structures of canine CK isoenzymes and to elucidate the mechanism of regulation in their expression, CK cDNA clones from d...
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.82.24.8394
更新日期:1985-12-01 00:00:00
abstract::Inherited colorectal cancer syndromes in humans exhibit regional specificity for tumor formation. By using mice with germline mutations in the adenomatous polyposis coli gene (Apc) and/or DNA mismatch repair genes, we have analyzed the genetic control of tumor regionality in the mouse small intestine. In C57BL/6 mice ...
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.0403338101
更新日期:2004-06-29 00:00:00
abstract::Binding enhancement by tertiary interactions is a strategy that takes advantage of the higher order folding of functionally important RNAs to bind short nucleic acid-based compounds tightly and more specifically than possible by simple base pairing. For example, tertiary interactions enhance binding of specific hexame...
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.96.6.2734
更新日期:1999-03-16 00:00:00
abstract::Several nonclassical major histocompatibilty antigens (class Ib molecules) have emerged as key players in the early immune response to pathogens or stress. Class Ib molecules activate subsets of T cells that mount effector responses before the adaptive immune system, and thus are called innate T cells. MR1 is a novel ...
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.0903196106
更新日期:2009-05-19 00:00:00
abstract::Human T-cell leukemia virus type I (HTLV-I) is a causative agent of adult T-cell leukemia (ATL). To elucidate the role of HTLV-I in leukemogenesis, we examined the biological activity of a defective HTLV-I provirus with the env-pX 3' long terminal repeat region cloned from leukemic cells of an ATL patient. Transfectio...
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.87.3.1071
更新日期:1990-02-01 00:00:00
abstract::H-NS and Lsr2 are nucleoid-associated proteins from Gram-negative bacteria and Mycobacteria, respectively, that play an important role in the silencing of horizontally acquired foreign DNA that is more AT-rich than the resident genome. Despite the fact that Lsr2 and H-NS proteins are dissimilar in sequence and structu...
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.1102544108
更新日期:2011-06-28 00:00:00
abstract::By Southern blotting and hybridization analysis using 32P-labeled poly(dT-dG) . poly(dC-dA) as a probe, we have found, in eukaryotic genomes, a huge number of stretches of dT-dG alternating sequence, a sequence that has been shown to adopt the Z-DNA conformation under some conditions. This sequence was found in all eu...
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.79.21.6465
更新日期:1982-11-01 00:00:00
abstract::In a search for a model cell system that might allow studies of the function of the Rho-related GTPase CDC42Hs in human cells, we measured the content and distribution of CDC42Hs in monocytes that were differentiating into macrophages. The total content of this protein increased 5- to 6-fold in phorbol ester-treated h...
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.91.10.4263
更新日期:1994-05-10 00:00:00
abstract::Fluorescence imaging in the second near-infrared window (NIR-II, 1,000-1,700 nm) features deep tissue penetration, reduced tissue scattering, and diminishing tissue autofluorescence. Here, NIR-II fluorescent probes, including down-conversion nanoparticles, quantum dots, single-walled carbon nanotubes, and organic dyes...
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.1521175113
更新日期:2016-05-10 00:00:00
abstract::We have measured the fidelity of bidirectional, semiconservative DNA synthesis by a human DNA replication complex in vitro. Replication was performed by extracts of HeLa cells in the presence of simian virus 40 (SV40) large tumor antigen by using a double-stranded phage M13mp2 DNA template containing the SV40 origin o...
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.85.19.7064
更新日期:1988-10-01 00:00:00
abstract::Chlorarachniophytes are amoeboid algae with unusual chloroplasts. Instead of the usual two membranes that surround the chloroplasts of plants, green algae, and red algae, the chloroplasts of chlorarachniophytes have four bounding membranes. The extra membranes may reflect an unusual origin of chlorarachniophyte chloro...
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.91.9.3690
更新日期:1994-04-26 00:00:00
abstract::The genomes of hyperthermophilic Archaea encode dozens of methylation guide, C/D box small RNAs that guide 2'-O-methylation of ribose to specific sites in rRNA and various tRNAs. The genes encoding the Sulfolobus homologues of eukaryotic proteins that are known to be present in C/D box small nucleolar ribonucleoprotei...
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.082101999
更新日期:2002-04-16 00:00:00
abstract::Neuroblastoma-glioma hybrid cells (NG108-15) in suspension accumulate the permeant lipophilic cation [(3)H]tetraphenylphosphonium (TPP(+)) against a concentration gradient. The steady-state level of TPP(+) accumulation is about twice as great in physiological media of low K(+) concentration (i.e., 5 mM K(+)/135 mM Na(...
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.76.2.650
更新日期:1979-02-01 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::Glutamyl-tRNA (Glu-tRNA), formed by Glu-tRNA synthetase (GluRS), is a substrate for protein biosynthesis and tetrapyrrole formation by the C(5) pathway. In this route Glu-tRNA is transformed to delta-aminolevulinic acid, the universal precursor of tetrapyrroles (e.g., heme and chlorophyll) by the action of Glu-tRNA 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.0611611104
更新日期:2007-02-27 00:00:00
abstract::NAPVSIPQ (NAP), an active fragment of the glial-derived activity-dependent neuroprotective protein, is protective at femtomolar concentrations against a wide array of neural insults and prevents ethanol-induced fetal wastage and growth retardation in mice. NAP also antagonizes ethanol inhibition of L1-mediated cell 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.1331636100
更新日期:2003-07-08 00:00:00
abstract::In response to various pathological stresses, the heart undergoes a pathological remodeling process that is associated with cardiomyocyte hypertrophy. Because cardiac hypertrophy can progress to heart failure, a major cause of lethality worldwide, the intracellular signaling pathways that control cardiomyocyte growth ...
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.0701099104
更新日期:2007-06-12 00:00:00
abstract::Heparin is the most widely prescribed biopharmaceutical in production globally. Its potent anticoagulant activity and safety makes it the drug of choice for preventing deep vein thrombosis and pulmonary embolism. In 2008, adulterated material was introduced into the heparin supply chain, resulting in several hundred d...
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.1920880117
更新日期:2020-04-28 00:00:00
abstract::We have isolated from vaccinia virus cores an enzyme, 5'-phosphate-polyribonucleotide kinase, that in the presence of ATP and Mg2+ catalyzes the conversion of 5'-phosphate and 5'-diphosphate termini of RNA to the 5'-triphosphate species. With the exception of dATP, other nucleoside triphosphates were inactive as phosp...
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.75.10.4793
更新日期:1978-10-01 00:00:00
abstract::Murine mammary tumor virus (MMTV) expression is analyzed in a T-lymphoid cell line (T1M1) sensitive to the killing effect of glucocorticoids and in two of its variants, one resistant (T1M1r) and one supersensitive (T1M1ss) to glucocorticoid-induced lymphocytolysis. In the T1M1 line, MMTV is expressed and induced appro...
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.80.1.110
更新日期:1983-01-01 00:00:00
abstract::Conjugative DNA transfer of the self-transmissible broad-host-range plasmid RP4 is initiated by strand- and site-specific cleavage at the nick site (nic) of the transfer origin (oriT). Cleavage results in covalent attachment of the plasmid-encoded relaxase (TraI) to the 5'-terminal 2'-deoxycytidine residue at nic. We ...
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.90.7.2925
更新日期:1993-04-01 00:00:00
abstract::2(S)-dihydroxypropanesulfonate (DHPS) is a microbial degradation product of 6-deoxy-6-sulfo-d-glucopyranose (sulfoquinovose), a component of plant sulfolipid with an estimated annual production of 1010 tons. DHPS is also at millimolar levels in highly abundant marine phytoplankton. Its degradation and sulfur recycling...
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.2003434117
更新日期:2020-07-07 00:00:00
abstract::It is generally believed that the old quantum theory, as presented by Niels Bohr in 1913, fails when applied to few electron systems, such as the H(2) molecule. Here, we find previously undescribed solutions within the Bohr theory that describe the potential energy curve for the lowest singlet and triplet states of H(...
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.0505778102
更新日期:2005-08-23 00:00:00
abstract::The capsids of neurotropic herpesviruses have the remarkable ability to move in specific directions within axons. By modulating bidirectional capsid transport to favor either retrograde (minus-end) or anterograde (plus-end) motion, these viruses travel to sensory ganglia or peripheral tissue at specific stages of infe...
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.0500803102
更新日期:2005-04-19 00:00:00
abstract::A fundamental problem in cell biology is to understand how spatial information is recognized and integrated into morphogenetic responses. Budding yeast undergoes differentiation to filamentous growth, which involves changes in cell polarity through mechanisms that remain obscure. Here we define a regulatory input wher...
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.1522679113
更新日期:2016-04-05 00:00:00
abstract::Tissue kallikrein (TK) is a serine protease synthetized in renal tubular cells located upstream from the collecting duct where renal potassium balance is regulated. Because secretion of TK is promoted by K+ intake, we hypothesized that this enzyme might regulate plasma K+ concentration ([K+]). We showed in wild-type m...
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.0913070107
更新日期:2010-07-27 00:00:00
abstract::CD4-expressing T cells in lymphoid organs are infected by the primary strains of HIV and represent one of the main sources of virus replication. Gene therapy strategies are being developed that allow the transfer of exogenous genes into CD4(+) T lymphocytes whose expression might prevent viral infection or replication...
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.94.16.8640
更新日期:1997-08-05 00:00:00
abstract::Wnt and Shh signaling pathways are critical for the development and maturation of many epithelial tissues. Both pathways have roles in stem cell maintenance, tissue development, and tumorigenesis. However, linkage between these pathways in mammalian systems had not been well established. Here, we report that Shh expre...
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.0607399104
更新日期:2007-02-13 00:00:00
abstract::Fetal pancreatic beta cells demonstrate a deficient insulin release in response to glucose, but the underlying mechanism at the cellular level is unknown. By using beta cells from 21-day fetal rats we made an attempt to clarify the mechanism(s) behind this reduced glucose response. In addition to measuring insulin rel...
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.86.12.4505
更新日期:1989-06-01 00:00:00
abstract::In epithelia, a primary damage of tight junctions (TJ) always leads to a secondary disruption of adherens junction (AJ), and vice versa. This response, if occurring in the testis, would disrupt spermatogenesis because the blood-testis barrier (BTB) must remain intact during the transit of spermatids in the seminiferou...
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.1001823107
更新日期:2010-06-22 00:00:00