The Experts below are selected from a list of 591123 Experts worldwide ranked by ideXlab platform
Toshi Shioda - One of the best experts on this subject based on the ideXlab platform.
-
cbp p300 interacting protein cited1 modulates parathyroid hormone regulation of osteoblastic differentiation
Endocrinology, 2008Co-Authors: Dehong Yang, P Divieti, Toshi Shioda, Richard F BringhurstAbstract:PTH regulates osteoblastic differentiation and activity and exerts different overall skeletal effects in vivo, depending on the schedule and dose of administration. In clonal Wt9 murine osteoblastic cells, mRNA and protein levels of CITED1 transcriptional coactivator were strongly up-regulated by human (h) PTH(1–34). Stimulation of CITED1 mRNA by PTH was transient, peaking at 4 h, concentration dependent, and blocked by actinomycin D but not cycloheximide. The stimulation was mimicked by forskolin, phorbol ester, and the cAMP-selective PTH analog [G1,R19] hPTH (1–28) and inhibited completely by the protein kinase A inhibitor, H89 and partially by phorbol ester-induced protein kinase C depletion. Increased CITED1 expression was not maintained during persistent (24 h) PTH exposure. Cultured primary calvarial osteoblasts from neonatal homozygous or hemizygous CITED1-knockout (KO) mice achieved 2-fold greater mineralized nodule formation in comparison with wild type (WT) osteoblasts. This effect was blocked by restoration of CITED1 expression via adenoviral gene transfer. Intermittent administration of hPTH(1–34) (10 nm, for 4 h every 48 h) for 3–6 wk increased mineralization up to 2-fold over basal levels in both WT and CITED1 KO mouse calvarial cell cultures. Whereas the cAMP-selective [G1,R19]hPTH(1–28) analog [at 100 nm, equivalent to 10 nm hPTH(1–34)] did not stimulate mineralization in WT cultures, it was twice as effective as hPTH(1–34) in CITED1 KO cultures. Thus, CITED1 negatively regulates osteoblastic differentiation in vitro and inhibits the cAMP-dependent stimulation of differentiation by intermittent PTH. We conclude also that PTH receptor signaling pathways independent of cAMP restrain osteoblastic differentiation, an effect normally obscured in the presence of CITED1 but revealed in its absence.
-
eralpha cited1 co regulated genes expressed during pubertal mammary gland development implications for breast cancer prognosis
Oncogene, 2007Co-Authors: J Mcbryan, P A Kenny, Jillian Howlin, Toshi ShiodaAbstract:Expression microarray analysis identified over 930 genes regulated during puberty in the mouse mammary gland. Most prominent were genes whose expression increased in parallel with pubertal development and remained high thereafter. Members of the Wnt, transforming growth factor-beta and oestrogen-signalling pathways were significantly overrepresented. Comparison to expression data from CITED1 knockout mice identified a subset of oestrogen-responsive genes displaying altered expression in the absence of CITED1. Included in this subset are stanniocalcin2 (Stc2) and amphiregulin (Areg). Chromatin immunoprecipitation revealed that ERalpha binds to oestrogen response elements in both the Stc2 and Areg genes in the mammary gland during puberty. Additionally, CITED1 and ERalpha localize to the same epithelial cells of the pubertal mammary gland, supporting a role for interaction of these two proteins during normal development. In a human breast cancer data set, expression of Stc2, Areg and CITED1 parallel that of ERalpha. Similar to ERalpha, CITED1 expression correlates with good outcome in breast cancer, implying that potential maintenance of the ERalpha-CITED1 co-regulated signalling pathway in breast tumours can indicate good prognosis. (Less)
-
eralpha cited1 co regulated genes expressed during pubertal mammary gland development implications for breast cancer prognosis
Oncogene, 2007Co-Authors: J Mcbryan, P A Kenny, Jillian Howlin, Toshi Shioda, Finian MartinAbstract:Expression microarray analysis identified over 930 genes regulated during puberty in the mouse mammary gland. Most prominent were genes whose expression increased in parallel with pubertal development and remained high thereafter. Members of the Wnt, transforming growth factor-beta and oestrogen-signalling pathways were significantly overrepresented. Comparison to expression data from CITED1 knockout mice identified a subset of oestrogen-responsive genes displaying altered expression in the absence of CITED1. Included in this subset are stanniocalcin2 (Stc2) and amphiregulin (Areg). Chromatin immunoprecipitation revealed that ERalpha binds to oestrogen response elements in both the Stc2 and Areg genes in the mammary gland during puberty. Additionally, CITED1 and ERalpha localize to the same epithelial cells of the pubertal mammary gland, supporting a role for interaction of these two proteins during normal development. In a human breast cancer data set, expression of Stc2, Areg and CITED1 parallel that of ERalpha. Similar to ERalpha, CITED1 expression correlates with good outcome in breast cancer, implying that potential maintenance of the ERalpha-CITED1 co-regulated signalling pathway in breast tumours can indicate good prognosis.
-
cited1 and CITED2 are differentially expressed in the developing kidney but are not required for nephrogenesis
Developmental Dynamics, 2007Co-Authors: Scott Boyle, Alan O. Perantoni, Toshi Shioda, Mark Ptde CaesteckerAbstract:Early kidney development in mammals is characterized by reciprocal tissue interaction between the ureteric bud and the metanephric mesenchyme. The coordinated response to this interaction is regulated largely at the transcriptional level. Here, we investigate the expression and function of Cited1, a transcriptional cofactor that we have previously implicated in kidney development. We show that Cited1 is expressed in the metanephric mesenchyme after invasion of the ureteric bud and that its expression is limited to the cap mesenchyme, those cells that aggregate most tightly around the tip of the ureteric bud and give rise to nephronic epithelium of the adult kidney. Cited1 is down-regulated during the initial stages of epithelial conversion and is not expressed past this progenitor stage. Despite its unique expression pattern, deletion of Cited1 does not disrupt kidney development. We hypothesized that this finding was due to functional redundancy with other members of this gene family. The expression pattern of CITED2 overlaps that of Cited1, but its deletion, either alone or in combination with Cited1, does not disrupt epithelial differentiation of the metanephric mesenchyme. From these studies, we conclude that Cited1 and 2 are dynamically expressed during kidney development, but are not required for nephrogenesis. Developmental Dynamics 236:2321–2330, 2007. © 2007 Wiley-Liss, Inc.
-
the transcriptional activity of cited1 is regulated by phosphorylation in a cell cycle dependent manner
Journal of Biological Chemistry, 2006Co-Authors: Scott Boyle, Sally L. Dunwoodie, Duncan B Sparrow, Toshi Shioda, Mark Ptde CaesteckerAbstract:Abstract CITED1 is the founding member of the CITED family of cofactors that are involved in regulating a wide variety of CBP/p300-dependent transcriptional responses. In the present study, we show that the phosphorylation status of CITED1 changes during the cell cycle and affects its transcriptional cofactor activity. Tryptic mapping and mutagenesis studies identified five phosphorylated serine residues in CITED1. Phosphorylation of these residues did not affect CRM1-dependent nuclear export, but did decrease CITED1 binding to p300 and inhibited CITED1-dependent transactivation of Smad4 and p300. These results suggest that CITED1 functions as a cell cycle-dependent transcriptional cofactor whose activity is regulated by phosphorylation.
Jillian Howlin - One of the best experts on this subject based on the ideXlab platform.
-
cited1 is a novel binding partner of mitf that influences the mitf directed transcriptional profile in melanoma
2017Co-Authors: Barbara Lettiero, åke Borg, Sofia K Gruvbergersaal, Goran Jonsson, Martin Lauss, Jillian HowlinAbstract:We previously demonstrated how CITED1 knockdown in melanoma cells had the capacity to perturb expression of a significant number of genes that comprised MITF and several of its known transcriptional targets. This manifest as a switch from a more invasive to a more proliferative gene signature phenotype. We now demonstrate by using MITF ChIP-seq, that altered CITED1 expression affects MITF transcription factor binding to its targets across the genome. We show that silencing CITED1 effectively amplifies the MITF chromatin-binding signal response while we also demonstrate for the first time that CITED1 and MITF co-localise in a nuclear complex using an in-situ ligation proximity assay. We propose that CITED1-MITF binding is capable of altering both the affinity of chromatin association and transcriptional response to MITF at the target regions in the genome where MITF is either directly or indirectly bound to DNA. As CITED1/SMAD2 has been shown to mediate TGFβ-driven transcription that induces amoeboid-like invasion in melanoma cells we hypothesis that the MITF/CITED1 driven transcriptional response dominates in MITF-high/low-invasive environment or proliferative signature cell phenotype, whereas the SMAD2/CITED1 transcriptional response is dominant in a low-MITF/ high-invasive signature environment.
-
loss of cited1 an mitf regulator drives a phenotype switch in vitro and can predict clinical outcome in primary melanoma tumours
PeerJ, 2015Co-Authors: Jillian Howlin, Helena Cirenajwis, Lao H Saal, åke Borg, Sofia K Gruvbergersaal, Johan Staaf, Barbara Lettiero, Martin Lauss, Goran JonssonAbstract:CITED1 is a non-DNA binding transcriptional co-regulator whose expression can distinguish the ‘proliferative’ from ‘invasive’ signature in the phenotype-switching model of melanoma. We have found that, in addition to other ‘proliferative’ signature genes, CITED1 expression is repressed by TGFβ while the ‘invasive’ signature genes are upregulated. In agreement, CITED1 positively correlates with MITF expression and can discriminate the MITF-high/pigmentation tumour molecular subtype in a large cohort (120) of melanoma cell lines. Interestingly, CITED1 overexpression significantly suppressed MITF promoter activation, mRNA and protein expression levels while MITF was transiently upregulated following siRNA mediated CITED1 silencing. Conversely, MITF siRNA silencing resulted in CITED1 downregulation indicating a reciprocal relationship. Whole genome expression analysis identified a phenotype shift induced by CITED1 silencing and driven mainly by expression of MITF and a cohort of MITF target genes that were significantly altered. Concomitantly, we found changes in the cell-cycle profile that manifest as transient G1 accumulation, increased expression of CDKN1A and a reduction in cell viability. Additionally, we could predict survival outcome by classifying primary melanoma tumours using our in vitro derived ‘CITED1-silenced’ gene expression signature. We hypothesize that CITED1 acts a regulator of MITF, functioning to maintain MITF levels in a range compatible with tumourigenesis.
-
eralpha cited1 co regulated genes expressed during pubertal mammary gland development implications for breast cancer prognosis
Oncogene, 2007Co-Authors: J Mcbryan, P A Kenny, Jillian Howlin, Toshi ShiodaAbstract:Expression microarray analysis identified over 930 genes regulated during puberty in the mouse mammary gland. Most prominent were genes whose expression increased in parallel with pubertal development and remained high thereafter. Members of the Wnt, transforming growth factor-beta and oestrogen-signalling pathways were significantly overrepresented. Comparison to expression data from CITED1 knockout mice identified a subset of oestrogen-responsive genes displaying altered expression in the absence of CITED1. Included in this subset are stanniocalcin2 (Stc2) and amphiregulin (Areg). Chromatin immunoprecipitation revealed that ERalpha binds to oestrogen response elements in both the Stc2 and Areg genes in the mammary gland during puberty. Additionally, CITED1 and ERalpha localize to the same epithelial cells of the pubertal mammary gland, supporting a role for interaction of these two proteins during normal development. In a human breast cancer data set, expression of Stc2, Areg and CITED1 parallel that of ERalpha. Similar to ERalpha, CITED1 expression correlates with good outcome in breast cancer, implying that potential maintenance of the ERalpha-CITED1 co-regulated signalling pathway in breast tumours can indicate good prognosis. (Less)
-
eralpha cited1 co regulated genes expressed during pubertal mammary gland development implications for breast cancer prognosis
Oncogene, 2007Co-Authors: J Mcbryan, P A Kenny, Jillian Howlin, Toshi Shioda, Finian MartinAbstract:Expression microarray analysis identified over 930 genes regulated during puberty in the mouse mammary gland. Most prominent were genes whose expression increased in parallel with pubertal development and remained high thereafter. Members of the Wnt, transforming growth factor-beta and oestrogen-signalling pathways were significantly overrepresented. Comparison to expression data from CITED1 knockout mice identified a subset of oestrogen-responsive genes displaying altered expression in the absence of CITED1. Included in this subset are stanniocalcin2 (Stc2) and amphiregulin (Areg). Chromatin immunoprecipitation revealed that ERalpha binds to oestrogen response elements in both the Stc2 and Areg genes in the mammary gland during puberty. Additionally, CITED1 and ERalpha localize to the same epithelial cells of the pubertal mammary gland, supporting a role for interaction of these two proteins during normal development. In a human breast cancer data set, expression of Stc2, Areg and CITED1 parallel that of ERalpha. Similar to ERalpha, CITED1 expression correlates with good outcome in breast cancer, implying that potential maintenance of the ERalpha-CITED1 co-regulated signalling pathway in breast tumours can indicate good prognosis.
-
cited1 homozygous null mice display aberrant pubertal mammary ductal morphogenesis
Oncogene, 2006Co-Authors: Jillian Howlin, J Mcbryan, Silvia Napoletano, Teresa Lambe, Emmett Mcardle, Toshi ShiodaAbstract:Expression microarray analysis identified CITED1 among a group of genes specifically upregulated in the pubertal mouse mammary gland. At puberty, CITED1 localizes to the luminal epithelial cell population of the mammary ducts and the body cells of the terminal end buds. Generation of CITED1 gene knockout mice showed that homozygous null mutants exhibit retarded mammary ductal growth at puberty and, in addition, dilated ductal structures with a lack of spatial restriction of the subtending branches. Analysis of CITED1 homozygous null and heterozygous null mammary gland gene expression using microarrays suggested that the mammary-specific phenotype seen in the homozygous null females is due to a disturbance in the transcription of a number of key mediators of pubertal ductal morphogenesis. These include estrogen and TGFbeta responsive genes, such as the EGFR/ErbB2 ligand, amphiregulin, whose transcription we suggest is directly or indirectly regulated by CITED1.
Andres M Lozano - One of the best experts on this subject based on the ideXlab platform.
-
highly cited works in neurosurgery part i the 100 top cited papers in neurosurgical journals a review
Journal of Neurosurgery, 2010Co-Authors: Francisco A Ponce, Andres M LozanoAbstract:Object The number of citations a published article receives is a measure of its impact in the scientific community. This study identifies and characterizes the current 100 top-cited articles in journals specifically dedicated to neurosurgery. Methods Neurosurgical journals were identified using the Institute for Scientific Information Journal Citation Reports. A search was performed using Institute for Scientific Information Web of Science for articles appearing in each of these journals. The 100 top-cited articles were selected and analyzed. Results The 100 most cited manuscripts in neurosurgical journals appeared in 3 of 13 journals dedicated to neurosurgery. These included 79 in the Journal of Neurosurgery, 11 in the Journal of Neurology, Neurosurgery and Psychiatry, and 10 in Neurosurgery. The individual citation counts for these articles ranged from 287 to 1515. Seventy-seven percent of articles were published between 1976 and 1995. Representation varied widely across neurosurgical disciplines, with ...
-
highly cited works in neurosurgery part i the 100 top cited papers in neurosurgical journals
Journal of Neurosurgery, 2010Co-Authors: Francisco A Ponce, Andres M LozanoAbstract:Object The number of citations a published article receives is a measure of its impact in the scientific community. This study identifies and characterizes the current 100 top-cited articles in journals specifically dedicated to neurosurgery. Methods Neurosurgical journals were identified using the Institute for Scientific Information Journal Citation Reports. A search was performed using Institute for Scientific Information Web of Science for articles appearing in each of these journals. The 100 top-cited articles were selected and analyzed. Results The 100 most cited manuscripts in neurosurgical journals appeared in 3 of 13 journals dedicated to neurosurgery. These included 79 in the Journal of Neurosurgery, 11 in the Journal of Neurology, Neurosurgery and Psychiatry, and 10 in Neurosurgery. The individual citation counts for these articles ranged from 287 to 1515. Seventy-seven percent of articles were published between 1976 and 1995. Representation varied widely across neurosurgical disciplines, with ...
Francisco A Ponce - One of the best experts on this subject based on the ideXlab platform.
-
highly cited works in neurosurgery part i the 100 top cited papers in neurosurgical journals a review
Journal of Neurosurgery, 2010Co-Authors: Francisco A Ponce, Andres M LozanoAbstract:Object The number of citations a published article receives is a measure of its impact in the scientific community. This study identifies and characterizes the current 100 top-cited articles in journals specifically dedicated to neurosurgery. Methods Neurosurgical journals were identified using the Institute for Scientific Information Journal Citation Reports. A search was performed using Institute for Scientific Information Web of Science for articles appearing in each of these journals. The 100 top-cited articles were selected and analyzed. Results The 100 most cited manuscripts in neurosurgical journals appeared in 3 of 13 journals dedicated to neurosurgery. These included 79 in the Journal of Neurosurgery, 11 in the Journal of Neurology, Neurosurgery and Psychiatry, and 10 in Neurosurgery. The individual citation counts for these articles ranged from 287 to 1515. Seventy-seven percent of articles were published between 1976 and 1995. Representation varied widely across neurosurgical disciplines, with ...
-
highly cited works in neurosurgery part i the 100 top cited papers in neurosurgical journals
Journal of Neurosurgery, 2010Co-Authors: Francisco A Ponce, Andres M LozanoAbstract:Object The number of citations a published article receives is a measure of its impact in the scientific community. This study identifies and characterizes the current 100 top-cited articles in journals specifically dedicated to neurosurgery. Methods Neurosurgical journals were identified using the Institute for Scientific Information Journal Citation Reports. A search was performed using Institute for Scientific Information Web of Science for articles appearing in each of these journals. The 100 top-cited articles were selected and analyzed. Results The 100 most cited manuscripts in neurosurgical journals appeared in 3 of 13 journals dedicated to neurosurgery. These included 79 in the Journal of Neurosurgery, 11 in the Journal of Neurology, Neurosurgery and Psychiatry, and 10 in Neurosurgery. The individual citation counts for these articles ranged from 287 to 1515. Seventy-seven percent of articles were published between 1976 and 1995. Representation varied widely across neurosurgical disciplines, with ...
Richard F Bringhurst - One of the best experts on this subject based on the ideXlab platform.
-
nuclear translocation of cbp p300 interacting protein cited1 induced by parathyroid hormone requires serine phosphorylation at position 79 in its 63 84 domain
Cellular Signalling, 2014Co-Authors: Ruiqiang Feng, Zhaozong Fu, Richard F Bringhurst, Yue Meng, Liang Yuan, Junqing Li, Dehong YangAbstract:Abstract The transcriptional cofactor CITED1 inhibits osteoblastic differentiation and blunts the stimulation of osteoblastic differentiation by parathyroid hormone (PTH). In the MC3T3-E1 osteoblastic cell line, we found that CITED1 was located predominantly in the cytoplasm and that hPTH(1–34) increased translocation of CITED1 from the cytoplasm to the nucleus. This response to hPTH(1–34) was not observed when all 9 serine residues within the 63–84 domain of CITED1 were mutated to alanines (CITED1 9S>A) or when a single serine to alanine mutation was made at position 79 (CITED1 S 79 >A). CITED1 containing mutations of these 9 serines to glutamic acid (9S>E) retained the same nuclear translocation response to hPTH(1–34) as the wild type CITED1. ALP activity and formation of mineralized nodules were inhibited in cells transfected with pcDNA3-CFP-CITED1 or with pcDNA3-CFP-CITED1 9S>E with or without hPTH(1–34) treatment (all P A. Cells exposed to intermittent treatment with hPTH(1–34) expressed more ALP2, Runx2 and osteocalcin than vehicle-treated cells. These effects of hPTH(1–34) were inhibited in cells transfected with pcDNA3-CFP-CITED1 or pcDNA3-CFP-CITED1 9S>E, but were slightly enhanced by the alanine mutants. PKC activator (TPA) increased nuclear translocation of CITED1, whereas a PKC inhibitor (Go6983) blunted the effect of hPTH(1–34) on the nuclear translocation of wildtype CITED1 but not of CITED1 S 79 >E. The data indicated that serine phosphorylation at position 79 in the 63–84 domain is associated with PKC activation, and is required for both CITED1 nuclear translocation induced by PTH and the negative effects of CITED1 on osteoblastic differentiation and mineralization.
-
cbp p300 interacting protein cited1 modulates parathyroid hormone regulation of osteoblastic differentiation
Endocrinology, 2008Co-Authors: Dehong Yang, P Divieti, Toshi Shioda, Richard F BringhurstAbstract:PTH regulates osteoblastic differentiation and activity and exerts different overall skeletal effects in vivo, depending on the schedule and dose of administration. In clonal Wt9 murine osteoblastic cells, mRNA and protein levels of CITED1 transcriptional coactivator were strongly up-regulated by human (h) PTH(1–34). Stimulation of CITED1 mRNA by PTH was transient, peaking at 4 h, concentration dependent, and blocked by actinomycin D but not cycloheximide. The stimulation was mimicked by forskolin, phorbol ester, and the cAMP-selective PTH analog [G1,R19] hPTH (1–28) and inhibited completely by the protein kinase A inhibitor, H89 and partially by phorbol ester-induced protein kinase C depletion. Increased CITED1 expression was not maintained during persistent (24 h) PTH exposure. Cultured primary calvarial osteoblasts from neonatal homozygous or hemizygous CITED1-knockout (KO) mice achieved 2-fold greater mineralized nodule formation in comparison with wild type (WT) osteoblasts. This effect was blocked by restoration of CITED1 expression via adenoviral gene transfer. Intermittent administration of hPTH(1–34) (10 nm, for 4 h every 48 h) for 3–6 wk increased mineralization up to 2-fold over basal levels in both WT and CITED1 KO mouse calvarial cell cultures. Whereas the cAMP-selective [G1,R19]hPTH(1–28) analog [at 100 nm, equivalent to 10 nm hPTH(1–34)] did not stimulate mineralization in WT cultures, it was twice as effective as hPTH(1–34) in CITED1 KO cultures. Thus, CITED1 negatively regulates osteoblastic differentiation in vitro and inhibits the cAMP-dependent stimulation of differentiation by intermittent PTH. We conclude also that PTH receptor signaling pathways independent of cAMP restrain osteoblastic differentiation, an effect normally obscured in the presence of CITED1 but revealed in its absence.