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Min-Jue Xie, Yasuyuki Ishikawa, Hideshi Yagi, Tokuichi Iguchi, Yuichiro Oka, Kazuki Kuroda, Keiko Iwata, Hiroshi Kiyonari, Shinji Matsuda, Hideo Matsuzaki, Michisuke Yuzaki, Yugo Fukazawa, Makoto Sato
The essential involvement of phosphoinositides in synaptic plasticity is well-established, but incomplete knowledge of the downstream molecular entities prevents us from understanding their signalling cascades completely. Here, we determined that Phldb2, of which pleckstrin-homology domain is highly sensitive to PIP3 , functions as a phosphoinositide-signalling mediator for synaptic plasticity. BDNF application caused Phldb2 recruitment toward postsynaptic membrane in dendritic spines, whereas PI3K inhibition resulted in its reduced accumulation...
March 13, 2019: Scientific Reports
Geng Chen, Tong Zhou, Yang Li, Zhenxiang Yu, Liankun Sun
miR-29c-3p is a potential tumor suppressor microRNA that is reportedly downregulated in several types of human cancers, but its role in colon cancer remains to be elucidated. Meanwhile, TP53, one of the most important tumor suppressors, is highly mutated in colon cancer. In the attempt to connect p53 and miR-29c-3p, we found that the upstream of miR-29c-3p gene contains a functional p53 consensus responsive element that is driven by p53 transcriptional factor activity, suggesting miR-29c-3p as a direct p53 target gene...
May 20, 2017: Biochemical and Biophysical Research Communications
Boon Cheng Lim, Shinji Matsumoto, Hideki Yamamoto, Hiroki Mizuno, Junichi Kikuta, Masaru Ishii, Akira Kikuchi
Prickle is known to be involved in planar cell polarity, including convergent extension and cell migration; however, the detailed mechanism by which Prickle regulates cellular functions is not well understood. Here, we show that Prickle1 regulates front-rear polarization and migration of gastric cancer MKN1 cells. Prickle1 preferentially accumulated at the cell retraction site in close proximity to paxillin at focal adhesions. Prickle1 dynamics correlated with those of paxillin during focal adhesion disassembly...
August 15, 2016: Journal of Cell Science
Isamu Hoshino, Yasunori Akutsu, Kentaro Murakami, Naoki Akanuma, Yuka Isozaki, Tetsuro Maruyama, Takeshi Toyozumi, Yasunori Matsumoto, Hiroshi Suito, Masahiko Takahashi, Nobufumi Sekino, Aki Komatsu, Takayoshi Suzuki, Hisahiro Matsubara
BACKGROUND: The expression of genes can be influenced by the balance of histone acetylation and/or histone demethylation, with an imbalance of these processes possibly observed in many cancers. The histone demethylase LSD1 inhibitor activity is associated with selective transcriptional regulation and alterations in the gene expression. However, the exact mechanisms underlying the antitumor effects of LSD1 inhibitors are not fully understood. METHODS: The antitumor effects of NCL1, an LSD1 inhibitor, in esophageal squamous cell cancer (ESCC) cell lines were evaluated...
January 2016: Annals of Surgical Oncology
Andrius Baskys
Treatment of hypertension reduces vascular dementia (VaD) risk but not all anti-hypertensive drugs (AHDs) are equally effective, suggesting drug-gene interactions. To understand this relationship, publicly accessible databases were searched for genes deregulated in VaD and their interactions with AHDs. Genes that were downregulated in association with VaD were MTHFR, SYK, AGT, and RPGRIP1L. Genes that were upregulated in VaD were MMP9 and VEGFA. TNFSF14, AR, and PHLDB2 were also associated with VaD, however, transcription or protein level changes could not be ascertained...
2014: Journal of Alzheimer's Disease: JAD
Veronica Astro, Sara Chiaretti, Elisa Magistrati, Marc Fivaz, Ivan de Curtis
Cell migration during development and metastatic invasion requires the coordination of actin and adhesion dynamics to promote protrusive activity at the front of the cell. The knowledge of the molecular mechanisms required to achieve such coordination is fragmentary. Here, we identify a new functional complex that drives cell motility. ERC1a (an isoform of ERC1) and the LL5 proteins LL5α and LL5β (encoded by PHLDB1 and PHLDB2, respectively) are required, together with liprin-α1, for effective migration and tumor cell invasion, and do so by stabilizing the protrusive activity at the cell front...
September 1, 2014: Journal of Cell Science
Samantha J Stehbens, Matthew Paszek, Hayley Pemble, Andreas Ettinger, Sarah Gierke, Torsten Wittmann
Turnover of integrin-based focal adhesions (FAs) with the extracellular matrix (ECM) is essential for coordinated cell movement. In collectively migrating human keratinocytes, FAs assemble near the leading edge, grow and mature as a result of contractile forces and disassemble underneath the advancing cell body. We report that clustering of microtubule-associated CLASP1 and CLASP2 proteins around FAs temporally correlates with FA turnover. CLASPs and LL5β (also known as PHLDB2), which recruits CLASPs to FAs, facilitate FA disassembly...
June 2014: Nature Cell Biology
Amin Sabri, Donna Lai, Arlene D'Silva, Sean Seeho, Jasjot Kaur, Cecilia Ng, Jon Hyett
INTRODUCTION: Extremes of fetal growth are associated with increased perinatal mortality and morbidity and a higher prevalence of cardiovascular disease, obesity and diabetes in later life. We aimed to identify changes in placental gene expression in pregnancies with evidence of growth dysfunction and candidate genes that may be used to identify abnormal patterns of growth prior to delivery. METHODS: Growth-restricted (n = 4), macrosomic (n = 6) and normal term (n = 5) placentas were selected from a banked series (n = 200) collected immediately after caesarean section...
2014: Fetal Diagnosis and Therapy
Chaeyoung Lee, Younyoung Kim
Genetic basis for vascular dementia (VD) as a typical complex disease has been limitedly reported from association studies conducted with candidate genes. Even recent genomewide association studies (GWAS) could hardly identify additional genetic factors for VD. Although a considerable complexity for its genetic architecture was suspected, there were some challenges to identify false negative associations that resulted from the GWAS. Challenges to identifying genetic factors and their functions after the trials of GWAS revealed that splicing of primary transcript was inhibited (SYK) or delayed (PHLDB2) by a nucleotide substitution of the corresponding gene...
March 1, 2013: Gene
Zu-Yau Lin, Wan-Long Chuang
The common genes responsible for the characteristics of primary cultured invasive phenotype hepatocellular carcinoma (HCC) cells were investigated. Primary cultured HCC cells from three patients were separated by Matrigel invasion into parent and invasive cells. Whole human genome oligo microarray was applied to detect the differentially expressed genes in invasive cells. A purchased HCC cell line (HA 22T/VGH) was studied for comparison. Forty genes were consistently up-regulated and 14 genes were consistently down-regulated among primary cultured invasive cells...
September 2012: Biomedicine & Pharmacotherapy
Sangmi Eom, Chaeyoung Lee
OBJECTIVES: A genome-wide association study (GWAS) failed to detect any genetic associations with susceptibility to vascular dementia (VaD) by the Bonferroni multiple test. This study aimed to discover false negative associations from the GWAS. METHODS: We selected a candidate gene in which multiple associations were identified with its single nucleotide polymorphisms (SNPs). Genetic associations were intensively examined with its SNPs using 207 VaD patients and 207 age- and sex-matched control subjects...
April 2013: World Journal of Biological Psychiatry
Qiong L Zhou, Zhen Y Jiang, Allan S Mabardy, Claudia M Del Campo, David G Lambright, John Holik, Kevin E Fogarty, Juerg Straubhaar, Sarah Nicoloro, Anil Chawla, Michael P Czech
Protein kinase B/Akt protein kinases control an array of diverse functions, including cell growth, survival, proliferation, and metabolism. We report here the identification of pleckstrin homology-like domain family B member 1 (PHLDB1) as an insulin-responsive protein that enhances Akt activation. PHLDB1 contains a pleckstrin homology domain, which we show binds phosphatidylinositol PI(3,4)P(2), PI(3,5)P(2), and PI(3,4,5)P(3), as well as a Forkhead-associated domain and coiled coil regions. PHLDB1 expression is increased during adipocyte differentiation, and it is abundant in many mouse tissues...
September 3, 2010: Journal of Biological Chemistry
A Carles, R Millon, A Cromer, G Ganguli, F Lemaire, J Young, C Wasylyk, D Muller, I Schultz, Y Rabouel, D Dembélé, C Zhao, P Marchal, C Ducray, L Bracco, J Abecassis, O Poch, B Wasylyk
Head and neck squamous cell carcinoma (HNSCC) is common worldwide and is associated with a poor rate of survival. Identification of new markers and therapeutic targets, and understanding the complex transformation process, will require a comprehensive description of genome expression, that can only be achieved by combining different methodologies. We report here the HNSCC transcriptome that was determined by exhaustive differential display (DD) analysis coupled with validation by different methods on the same patient samples...
March 16, 2006: Oncogene
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