Signal transduction insights最新文献

Decoding of Finger Millet Genome: A Milestone of Millet Genomics 小米基因组的解码:小米基因组学的里程碑

Signal transduction insights Pub Date : 2019-01-01 DOI: 10.1177/1178643418820541

S. Pandian, M. Ramesh

引用次数: 6

Tamoxifen Action in ER-Negative Breast Cancer 他莫昔芬对er阴性乳腺癌的作用

Signal transduction insights Pub Date : 2016-02-10 DOI: 10.4137/STI.S29901

S. Manna, M. Holz

引用次数: 73

Aberrant expression of cyclin D1 in cancer. 肿瘤细胞周期蛋白D1的异常表达。

Signal transduction insights Pub Date : 2015-09-20 DOI: 10.4137/STI.S30306

Kazushi Inoue, Elizabeth A. Fry

{"title":"Aberrant expression of cyclin D1 in cancer.","authors":"Kazushi Inoue, Elizabeth A. Fry","doi":"10.4137/STI.S30306","DOIUrl":"https://doi.org/10.4137/STI.S30306","url":null,"abstract":"Cyclin D1 binds and activates cyclin-dependent kinases 4/6 (Cdk4/6) to phosphorylate the retinoblastoma (RB) family proteins, relieving E2F/DPs from the negative restraint of RB proteins and histone deacetylases. The cyclin D-Cdk4/6 complexes activate cyclin E/Cdk2 through titration of the Cdk inhibitors p21Cip1/p27Kip1. Cyclin E/Cdk2 further phosphorylates RBs, thereby activating E2F/DPs, and cells enter the S phase of the cell cycle. Cyclin D-Cdk4/6 also phosphorylates MEP50 subunit of the protein arginine methyltransferase 5 (PRMT5), which cooperates with cyclin D1 to drive lymphomagenesis in vivo. Activated PRMPT5 causes arginine methylation of p53 to suppress expression of pro-apoptotic and anti-proliferative target genes, explaining the molecular mechanism for tumorigenesis. Cyclin D1 physically interacts with transcription factors such as estrogen receptor, androgen receptor, and Myb family proteins to regulate gene expression in Cdk-independent fashion. Dmp1 is a Myb-like protein that quenches the oncogenic signals from activated Ras or HER2 by inducing Arf/p53-dependent cell cycle arrest. Cyclin D1 binds to Dmp1α to activate both Arf and Ink4a promoters to induce cell cycle arrest or apoptosis in non-transformed cells to prevent them from neoplastic transformation. Dmp1-deficiency significantly accelerates mouse mammary tumorigenesis with reduced apoptosis and increased metastasis. Cyclin D1 interferes with ligand activation of PPARγ involved in cellular differentiation; it also physically interacts with histone deacetylases (HDACs) and p300 to repress gene expression. It has also been shown that cyclin D1 accelerates tumorigenesis through transcriptional activation of miR-17/20 and Dicer1 which, in turn, represses cyclin D1 expression. Identification of cyclin D1-binding proteins/promoters will be essential for further clarification of its biological activities.","PeriodicalId":89481,"journal":{"name":"Signal transduction insights","volume":"4 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2015-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/STI.S30306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70715631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 38

Signal Transduction Pathways Leading to Heat Shock Transcription. 导致热休克转录的信号转导途径。

Signal transduction insights Pub Date : 2010-01-01 DOI: 10.4137/STI.S3994

S K Calderwood, Y Xie, X Wang, M A Khaleque, S D Chou, A Murshid, T Prince, Y Zhang

{"title":"Signal Transduction Pathways Leading to Heat Shock Transcription.","authors":"S K Calderwood, Y Xie, X Wang, M A Khaleque, S D Chou, A Murshid, T Prince, Y Zhang","doi":"10.4137/STI.S3994","DOIUrl":"10.4137/STI.S3994","url":null,"abstract":"<p><p>Heat shock proteins (HSP) are essential for intracellular protein folding during stress and protect cells from denaturation and aggregation cascades that can lead to cell death. HSP genes are regulated at the transcriptional level by heat shock transcription factor 1 (HSF1) that is activated by stress and binds to heat shock elements in HSP genes. The activation of HSF1 during heat shock involves conversion from an inert monomer to a DNA binding trimer through a series of intramolecular folding rearrangements. However, the trigger for HSF1 at the molecular level is unclear and hypotheses for this process include reversal of feedback inhibition of HSF1 by molecular chaperones and heat-induced binding to large non-coding RNAs. Heat shock also causes a profound modulation in cell signaling pathways that lead to protein kinase activation and phosphorylation of HSF1 at a number of regulatory serine residues. HSP genes themselves exist in an accessible chromatin conformation already bound to RNA polymerase II. The RNA polymerase II is paused on HSP promoters after transcribing a short RNA sequence proximal to the promoter. Activation by heat shock involves HSF1 binding to the promoter and release of the paused RNA polymerase II followed by further rounds of transcriptional initiation and elongation. HSF1 is thus involved in both initiation and elongation of HSP RNA transcripts. Recent studies indicate important roles for histone modifications on HSP genes during heat shock. Histone modification occurs rapidly after stress and may be involved in promoting nucleosome remodeling on HSP promoters and in the open reading frames of HSP genes. Understanding these processes may be key to evaluating mechanisms of deregulated HSP expression that plays a key role in neurodegeneration and cancer.</p>","PeriodicalId":89481,"journal":{"name":"Signal transduction insights","volume":"2 ","pages":"13-24"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115718/pdf/nihms-201230.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29948265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0