bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tristetraprolin recruits functional mRNA decay complexes to ARE sequences
Authors: Hau Heidi H. , Walsh Richard J. , Ogilvie Rachel L. , Williams Darlisha A. , Reilly Cavan S. , Bohjanen Paul R. 
Published: November 2006

AbstractAU‐rich elements (AREs) in the 3′ untranslated region (UTR) of numerous mammalian transcripts function as instability elements that promote rapid mRNA degradation. Tristetraprolin (TTP) is an ARE‐binding protein that promotes rapid mRNA decay through mechanisms that are poorly understood. A 31 nucleotide ARE sequences from the TNF‐alpha 3′ UTR promoted TTP‐dependent mRNA decay when it was inserted into the 3′ UTR of a beta‐globin reporter transcript, indicating that this short sequence was sufficient for TTP function. We used a gel shift assay to identify a TTP‐containing complex in cytoplasmic extracts from TTP‐transfected HeLa cells that bound specifically to short ARE sequences. This TTP‐containing complex also contained the 5′–3′ exonuclease Xrn1 and the exosome component PM‐scl75 because it was super‐shifted with anti‐Xrn1 or anti‐PMscl75 antibodies. RNA affinity purification verified that these proteins associated specifically with ARE sequences in a TTP‐dependent manner. Using a competition binding assay, we found that the TTP‐containing complex bound with high affinity to short ARE sequences from GM‐CSF, IL‐3, TNF‐alpha, IL‐2, and c‐fos, but did not bind to a U‐rich sequence from c‐myc, a 22 nucleotide poly U sequence or a mutated GM‐CSF control sequence. High affinity binding by the TTP‐containing complex correlated with TTP‐dependent deadenylation and decay of capped, polyadenylated transcripts in a cell‐free mRNA decay assay, suggesting that the TTP‐containing complex was functional. These data support a model whereby TTP functions to enhance mRNA decay by recruiting components of the cellular mRNA decay machinery to the transcript. J. Cell. Biochem. 100: 1477–1492, 2007. © 2006 Wiley‐Liss, Inc.
Sphingosylphosphorylcholine induces apoptosis of endothelial cells through reactive oxygen species‐mediated activation of ERK
Authors: Jeon Eun Su , Lee Mi Jeong , Sung Sang‐Min , Kim Jae Ho 
Published: November 2006

AbstractSphingosylphosphorylcholine (SPC) produces reactive oxygen species (ROS) in MS1 pancreatic islet endothelial cells. In the present study, we explored the physiological significance of the SPC‐induced ROS generation in endothelial cells. SPC induced cell death of MS1 cells at higher than 10 µM concentration through a caspase‐3‐dependent pathway. SPC treatment induced sustained activation of an extracellular signal‐regulated kinase (ERK), in contrast to transient activation of ERK in response to platelet‐derived growth factor (PDGF)‐BB, which stimulated proliferation of MS1 cells. Both the SPC‐induced cell death and ERK activation were abolished by pretreatment of the cells with the MEK inhibitor U0126 or by overexpression of a dominant negative mutant of MEK1 (DN‐MEK1). Pretreatment of the cells with N‐acetylcysteine, an antioxidant, completely prevented the SPC‐induced ROS generation, apoptosis, and ERK activation, whereas the ROS generation was not abrogated by treatment with U0126. Consistent with these results, SPC induced cell death of human umbilical vein endothelial cells (HUVECs) through ROS‐mediated activation of ERK. These results suggest that the SPC‐induced generation of ROS plays a crucial role in the cell death of endothelial cells through ERK‐dependent pathway. J. Cell. Biochem. 100: 1536–1547, 2007. © 2006 Wiley‐Liss, Inc.
Ubiquitin‐dependent proteolysis of trihydrophobin 1 (TH1) by the human papilloma virus E6‐associated protein (E6‐AP)
Authors: Yang Yanzhong , Liu Weicheng , Zou Weiying , Wang Hanzhou , Zong Hongliang , Jiang Jianhai , Wang Yanlin , Gu Jianxin 
Published: November 2006

AbstractHuman Papilloma virus E6‐associated protein (E6‐AP), which is known as an E3 ubiquitin ligase, mediates ubiquitination and subsequent degradation of a series of cellular proteins. In this paper, we identify here trihydrophobin 1 (TH1), an integral subunit of the human negative transcription elongation factor (NELF) complex, as a novel E6‐AP interaction protein and a target of E6‐AP‐mediated degradation. Overexpression of E6‐AP results in degradation of TH1 in a dose‐dependent manner, whereas knock‐down of endogenous E6‐AP elevates the TH1 protein level. TH1 protein turnover is substantially faster, compared to controls, in cells that overexpressed E6‐AP. Wild‐type E6‐AP promotes the ubiquitination of TH1, while a catalytically inactive point mutant of E6‐AP abolishes its ubiquitination. Furthermore, in vitro ubiquitination assay also demonstrates that TH1 can be ubiquitinated by E6‐AP. The degradation is blocked by treatment with proteasome inhibitor MG132. Herein, we provide strong evidence that TH1 is a specific substrate that is targeted for degradation through E6‐AP‐catalyzed polyubiquitination. J. Cell. Biochem. 101: 167–180, 2007. © 2006 Wiley‐Liss, Inc.
The experience of HIV/AIDS among rural women in the Northwestern United States: A qualitative analysis
Authors: Mphande‐Finn Joyce T. , Sommers‐Flanagan John 
Published: November 2006

AbstractThe unique experience of HIV/AIDS among rural women in the United
States was explored using qualitative interviews with 7 women who are
HIV positive. Based on these interviews, eight themes emerged. These
included (a) daily powerful emotions, (b) emotional and physical
abandonment, (c) romantic betrayal, (d) medical treatment issues, (e) loss
and grief, (f) appreciating a good support system, (g) renewed purpose for
living, and (h) personal growth and transformation. Results are discussed
with regard to future research and practice with rural women with
HIV/AIDS, with an emphasis on the importance of social support and
counseling opportunities in facilitating women's progress through the
emotional process associated with HIV/AIDS diagnosis and treatment.
© 2007 Wiley Periodicals, Inc.
Contributors to assessments of risk in intimate partner violence: How victims and professionals differ
Authors: Cattaneo Lauren Bennett 
Published: November 2006

AbstractThis article explores what factors contribute to victims' vs. victim advocates' assessments of risk of repeat intimate partner violence. A sample of 169 court‐involved victims and the advocates who conducted intake with them were asked to rate victims' risk of repeat abuse. Significant contributors to victim assessments were her level of post‐traumatic stress disorder symptoms, the batterer's general violence, whether she had been living with the batterer at the time of the offense, and the level of psychological abuse in the relationship. For advocates, significant contributors were the batterer's drug use, whether the batterer and victim had children in common, and the level of physical and psychological abuse in the relationship. Implications of these differences and directions for future study are discussed. © 2007 Wiley Periodicals, Inc.
The depiction of mental illnesses in children's television programs
Authors: Wahl Otto , Hanrahan Erin , Karl Kelly , Lasher Erin , Swaye Janel 
Published: November 2006

AbstractConcern has been expressed that negative attitudes toward people with mental illnesses begin to develop early in childhood. This study examines one of the possible sources of learning of such negative attitudes—children's television programs. Two hundred sixty‐nine (269) hours of children's television programming were videotaped, viewed, and rated. Nearly half the programs viewed contained use of mental health terms. Most of these terms were slang and disrespectful (e.g., crazy and nut) and were used to disparage others. Twenty‐ one (21) characters with a mental illness were identified. These characters tended to be depicted as aggressive and threatening, and other characters responded to them with fear, exclusion, and disrespect. Children's television programs seem to provide substantial opportunity for children to develop negative attitudes and behaviors toward those with mental illnesses. © 2007 Wiley Periodicals, Inc.
Features that determine telomere homolog oligonucleotide‐induced therapeutic DNA damage‐like responses in cancer cells
Authors: Ohashi Norio , Yaar Mina , Eller Mark S. , Truzzi Francesca , Gilchrest Barbara A. 
Published: November 2006

AbstractCancer is the second leading cause of death in the USA, with metastatic disease proving a particular management challenge. Treatment modalities for patients with metastatic disease are limited, and survival beyond 5 years is uncommon. We have reported that an 11‐base DNA oligonucleotide 100% homologous to the telomere 3′ overhang can induce apoptosis, senescence and/or differentiation of several types of malignant cells in vitro and in vivo, while having minimal effect on normal cells. We now report that 22 oligonucleotides, 9–20 bases in length, with or without a 5′ phosphate group and with varying homology (40–100%) to the 3′ overhang, inhibit growth and induce apoptosis of human cell lines derived from breast cancers, pancreatic and ovarian carcinomas, and malignant melanoma, lines that lack p53 and/or p16 and harbor a variety of other abnormalities in key regulatory signaling pathways. Cytosine (C) content adversely affected oligonucleotide efficacy, decreasing their effect on cellular apoptosis by ≥80%. These data confirm and expand our earlier work suggesting that such telomere homolog oligonucleotides (T‐oligos) target an innate anti‐cancer defense system in human cells and may provide an effective treatment for cancers of multiple different cellular origins and genetic profile. J. Cell. Physiol. 210: 582–595, 2007. © 2006 Wiley‐Liss, Inc.
IGF‐1 upregulates electroneutral K‐Cl cotransporter KCC3 and KCC4 which are differentially required for breast cancer cell proliferation and invasiveness
Authors: Hsu Yueh‐Mei , Chou Cheng‐Yang , Chen Helen H.W. , Lee Wen‐Ying , Chen Yih‐Fung , Lin Pin‐Wen , Alper Seth L. , Ellory J. Clive , Shen Meng‐Ru 
Published: November 2006

AbstractThe cellular function of electroneutral K‐Cl cotransport (KCC) is to regulate epithelial ion transport and osmotic homeostasis. Here we investigate the mechanisms by which insulin‐like growth factor 1 (IGF‐1) cooperates with KCC to modulate breast cancer biology. IGF‐1 stimulates KCC activity of MCF‐7 breast cancer cells in a dose‐ and time‐dependent manner. Increased KCC3 and KCC4 abundances contribute to IGF‐1‐enhanced KCC activity. Endogenous cellular invasiveness was modestly attenuated by KCC4‐specific siRNA and the residual invasiveness was much less sensitive to IGF‐1 stimulation. KCC3 knockdown significantly reduced basal growth rate and almost abolished IGF‐1‐stimulated cell proliferation. Consistently, MCF‐7 cells obtained advantage in cell proliferation and invasiveness by overexpression of KCC3 and KCC4, respectively. Blockade of gene transcription by actinomycin D abolished IGF‐1‐mediated increase in KCC3 and KCC4 mRNA, indicating that IGF‐1 increases KCC abundance through the regulation of KCC genes. IGF‐1 treatment triggered phosphatidylinositol 3‐kinase and mitogen‐activated protein kinase (MAPK) cascades which were differentially required for IGF‐1‐stimulated biosynthesis of KCC3 and KCC4. Loss‐of‐function mutations in KCC significantly inhibited the development and progression of xenograft tumor in SCID mice. The expression level of IGF‐1 and KCC polypeptides in the surgical specimens showed a good linear correlation, suggesting autocrine or paracrine IGF‐1 stimulation of KCC production in vivo. Among patients with early‐stage node‐negative breast cancer, disease‐free survival (DFS) and overall survival (OS) curves were significantly different based on IGF‐1 and KCC expression. Thus, we conclude that KCC activation by IGF‐1 plays an important role in IGF‐1 receptor signaling to promote growth and spread of breast cancer cells. J. Cell. Physiol. 210: 626–636, 2007. © 2006 Wiley‐Liss, Inc.
Potent stimulation of large‐conductance Ca2+‐activated K+ channels by rottlerin, an inhibitor of protein kinase C‐δ, in pituitary tumor (GH3) cells and in cortical neuronal (HCN‐1A) cells
Authors: Wu Sheng‐Nan , Wang Ya‐Jean , Lin Ming‐Wei 
Published: November 2006

AbstractThe effects of rottlerin, a known inhibitor of protein kinase C‐δ activation, on ion currents were investigated in pituitary tumor (GH3) cells. Rottlerin (0.3–100 µM) increased the amplitude of Ca2+‐activated K+ current (IK(Ca)) in a concentration‐dependent manner with an EC50 value of 1.7 µM. In intracellular perfusion with rottlerin (1 µM) or staurosporine (10 µM), phorbol 12‐myristate 13‐acetate‐induced inhibition of IK(Ca) in these cells was abolished. In cell‐attached mode, rottlerin applied on the extracellular side of the membrane caused activation of large‐conductance Ca2+‐activated K+ (BKCa) channels, and a further application of BAPTA‐AM (10 µM) to the bath had no effect on rottlerin‐stimulated channel activity. When cells were exposed to rottlerin, the activation curve of these channels was shifted to less positive potential with no change in the slope factor. Rottlerin increased BKCa‐channel activity in outside‐out patches. Its change in kinetic behavior of BKCa channels is primarily due to an increase in mean open time. With the aid of minimal kinetic scheme, a quantitative description of rottlerin stimulation on BKCa channels in GH3 cells was also provided. Under current‐clamp configuration, rottlerin (1 µM) decreased the firing of action potentials. IK(Ca) elicited by simulated action potential waveforms was enhanced by this compound. In human cortical HCN‐1A cells, rottlerin (1 µM) could also interact with the BKCa channel to stimulate IK(Ca). Therefore, rottlerin may directly activate BKCa channels in neurons or endocrine cells. J. Cell. Physiol. 210: 655–666, 2007. © 2006 Wiley‐Liss, Inc.
Multiple binding of methyl‐CpG and polycomb proteins in long‐term gene silencing events
Authors: Matarazzo M.R. , De Bonis M.L. , Strazzullo M. , Cerase A. , Ferraro M. , Vastarelli P. , Ballestar E. , Esteller M. , Kudo S. , D'Esposito M. 
Published: November 2006

AbstractEpigenetic regulation is involved in the maintenance of long‐term silencing phenomena, such as X‐inactivation and genomic imprinting in mammals. Gene repression is mediated by several mechanisms, such as histone modifications, DNA methylation, and recruitment of Polycomb proteins. To understand the mechanistic relationships between these mechanisms for stable gene silencing, we analyzed the mechanisms of X‐ and Y‐inactivation of the PAR2 gene SYBL1, previously showed to be regulated by concerted epigenetic mechanisms. Maintenance of stable repression occurs via the recruitment of both MBDPs and PRC2 complexes to SYBL1 promoter. Their binding is equally sensitive to defective DNA methylation seen in cells derived from ICF syndrome patients. Multiple occupancy is a feature shared within long‐term repressed genes, such as the X‐inactivated PGK1 and the imprinted IGF2. MBD2, MBD3, and MeCP2 occupy SYBL1 promoter simultaneously, as revealed by sequential ChIP. We did not find this co‐occurring binding when looked for members of PRC2 complex together with any of the methyl‐binding proteins. Furthermore, in co‐transfection assays, MECP2 can silence methylated SYBL1 promoter, whereas the mutated protein fails. However, RNA interference of endogenous MECP2 does not induce the expression of the inactive SYBL1 alleles, suggesting that its silencing activity can be replaced by the other methyl‐binding proteins. Our data suggest that maintenance of long‐term silencing involves multiple layers of epigenetic control functionally redundant. PRC2 and MBD proteins could collaborate to different phases of this process, the former possibly recruiting DNMTs to the silenced promoters, the latter dictating the lock of the transcription. J. Cell. Physiol. 210: 711–719, 2007. © 2006 Wiley‐Liss, Inc.
MAP kinase‐dependent, NF‐κB‐independent regulation of inhibitor of apoptosis protein genes by TNF‐α
Authors: Furusu Akira , Nakayama Kenji , Xu Qihe , Konta Tsuneo , Kitamura Masanori 
Published: November 2006

AbstractThe inhibitor of apoptosis protein (IAP) family of molecules regulates apoptotic processes triggered by various stimuli. However, the mechanisms involved in the regulation of the IAP genes are not fully understood. In this report, we examined roles of nuclear factor‐κB (NF‐κB) and mitogen‐activated protein (MAP) kinases in tumor necrosis factor‐α (TNF‐α)‐induced expression of IAP genes. In human endothelial cells, TNF‐α induced c‐IAP1 and c‐IAP2, but not XIAP and TIAP/Survivin, at the transcriptional level. Inactivation of NF‐κB by overexpression of a super‐repressor mutant of IκBα did not affect the induction of IAPs by TNF‐α. In contrast, extracellular signal‐regulated kinase, p38 MAP kinase, and c‐Jun N‐terminal kinase were activated after stimulation with TNF‐α, and inhibition of each kinase by PD098059, SB203580, curcumin, or SP600125 substantially attenuated the TNF‐α‐induced c‐IAP1 and c‐IAP2 expression. To examine whether the MAP kinases‐mediated induction of IAPs contributes to survival of TNF‐α‐exposed cells, cells were pretreated with MAP kinase inhibitors and stimulated with TNF‐α. Treatment with kinase inhibitors alone did not induce apoptosis but enhanced markedly TNF‐α‐triggered apoptosis. Furthermore, overexpression of either c‐IAP1 or c‐IAP2 diminished the apoptosis‐promoting effects of MAP kinase inhibitors. These data indicated that TNF‐α induced expression of c‐IAP1 and c‐IAP2 via MAP kinases, but not via NF‐κB, and that MAP kinases participated in the inhibition of apoptosis by induction of c‐IAPs in TNF‐α‐stimulated endothelial cells. J. Cell. Physiol. 210: 703–710, 2007. © 2006 Wiley‐Liss, Inc.
Molecular targets for retinal vascular diseases
Authors: Campochiaro Peter A. 
Published: November 2006

AbstractThe elucidation of the molecular pathogenesis of a disease in animal models provides candidate targets for treatment. As specific antagonists for a target are developed and tested in clinical trials, if benefit is achieved, the candidate becomes a validated target. Validated targets stimulate additional research to identify optimal ways of attacking the target and studies in related disease processes to determine if the molecule is also a target in that context. Vascular endothelial growth factor (VEGF) has been identified as a validated target for several retinal vascular diseases. This has led to a flurry of activity resulting in beneficial treatments for patients and intensification of the search for other targets. This review summarizes preclinical and clinical trial results obtained with VEGF antagonists and describes evidence supporting the candidacy of other molecules currently being tested or soon to be tested for target status. J. Cell. Physiol. 210: 575–581, 2007. © 2006 Wiley‐Liss, Inc.
Oncogenic KRAS provides a uniquely powerful and variable oncogenic contribution among RAS family members in the colonic epithelium
Authors: Keller Jeffrey W. , Franklin Jeffrey L. , Graves‐Deal Ramona , Friedman David B. , Whitwell Corbin W. , Coffey Robert J. 
Published: November 2006

AbstractActivating mutations of the RAS family of small GTPases are among the most common genetic events in human tumorigenesis. Constitutive activation of the three canonical family members, KRAS, NRAS, and HRAS segregate strongly by tissue type. Of these, KRAS mutations predominate in human tumors, including those arising from the colon and lung. We sought to compare the oncogenic contributions of different RAS isoforms in a comparable genetic setting and to explore downstream molecular changes that may explain the apparent differential oncogenic effects of the various RAS family members. We utilized colorectal cancer cell lines characterized by oncogenic KRAS in parallel with isogenically derived lines in which the mutant allele has been disrupted. We additionally attempted to reconstitute the isogenic derivatives with oncogenic forms of other RAS family members and analyze them in parallel. Pairwise analysis of HCT 116 and DLD‐1 cell lines as well as their isogenic derivatives reveals distinct K‐RASG13D signatures despite the genetic similarities of these cell lines. In DLD‐1, for example, oncogenic K‐RAS enhances the motility of these cells by downregulation of Rap1 activity, yet is not associated with increased ERK1/2 phosphorylation. In HCT 116, however, ERK1/2 phosphorylation is elevated relative to the isogenic derivative, but Rap1 activity is unchanged. K‐RAS is uniquely oncogenic in the colonic epithelium, though the molecular aspects of its oncogenic contribution are not necessarily conserved across cell lines. We therefore conclude that the oncogenic contribution of K‐RAS is a function of its multifaceted functionality and is highly context‐dependent. J. Cell. Physiol. 210: 740–749, 2007. © 2006 Wiley‐Liss, Inc.
Role of atypical protein kinase C isozymes and NF‐κB in IL‐1β‐induced expression of cyclooxygenase‐2 in human myometrial smooth muscle cells
Authors: Duggan Sara V. , Lindstrom Tamsin , Iglesias Teresa , Bennett Phillip R. , Mann Giovanni E. , Bartlett Simon R. 
Published: November 2006

AbstractIncreased myometrial expression of cyclooxygenase‐2 (Cox‐2) at term results from elevated local levels of inflammatory cytokines, and its inhibition provides a potential route for intervention in human pre‐term labor. We have identified a role for atypical protein kinase C (PKC) isozymes in IL‐1β‐induced Cox‐2 expression in human myometrial smooth muscle cells (HMSMC). The PKC inhibitor GF109203X (10 µM) inhibited IL‐1β‐induced Cox‐2 protein and RNA expression, which were also reduced by MAPK and nuclear factor κB (NF‐κB) inhibitors. GF109203X did not affect MAPK activities, and neither did it replicate the effect of p38 MAPK inhibition on Cox‐2 mRNA stability, suggesting that PKC operates through an independent mechanism. The effect of GF109203X remained intact after depletion of conventional and novel PKC isozymes by phorbol ester pre‐treatment. In contrast LY379196 (10 µM), which at micromolar concentrations inhibits all but atypical PKCs, did not affect Cox‐2 expression. A peptide corresponding to the pseudosubstrate sequence of atypical PKCs blocked Cox‐2 protein expression, whereas the sequence from conventional PKCs was ineffective. GF109203X did not affect NF‐κB binding to nuclear proteins, but strongly reduced NF‐κB‐dependent transcription in luciferase reporter assays. Our findings indicate that IL‐1β‐induced Cox‐2 expression in HMSMC in culture requires p38‐MAPK‐mediated mRNA stabilization and an independent activation of Cox‐2 transcription which is dependent on the action of atypical PKCs, probably through direct stimulation of the transactivating activity of NF‐κB. J. Cell. Physiol. 210: 637–643, 2007. © 2006 Wiley‐Liss, Inc.