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Latest Articles

  • NRF2-Dependent Bioactivation of Mitomycin C as a Novel Strategy To Target KEAP1-NRF2 Pathway Activation in Human Cancer
    Research Article
    NRF2-Dependent Bioactivation of Mitomycin C as a Novel Strategy To Target KEAP1-NRF2 Pathway Activation in Human Cancer

    Activating mutations in the KEAP1-NRF2 pathway are found in approximately 25% of lung tumors, where the hijacking of NRF2’s cytoprotective functions results in aggressive tumor growth, chemoresistance, and a poor prognosis for patients. There are currently no approved drugs which target aberrant NRF2 activation, which means that there is an urgent clinical need to target this orphan oncogenic pathway in human tumors. In this study, we...

    Liam Baird, Masayuki Yamamoto
  • Identification of Dominant Transcripts in Oxidative Stress Response by a Full-Length Transcriptome Analysis
    Research Article
    Identification of Dominant Transcripts in Oxidative Stress Response by a Full-Length Transcriptome Analysis

    Our body responds to environmental stress by changing the expression levels of a series of cytoprotective enzymes/proteins through multilayered regulatory mechanisms, including the KEAP1-NRF2 system. While NRF2 upregulates the expression of many cytoprotective genes, there are fundamental limitations in short-read RNA sequencing (RNA-Seq), resulting in confusion regarding interpreting the effectiveness of cytoprotective gene induction...

    Akihito Otsuki, Yasunobu Okamura, Yuichi Aoki, Noriko Ishida, Kazuki Kumada, Naoko Minegishi, Fumiki Katsuoka, Kengo Kinoshita, Masayuki Yamamoto
  • Open Access
    Circular RNA 100146 Promotes Colorectal Cancer Progression by the MicroRNA 149/HMGA2 Axis
    Research Article
    Circular RNA 100146 Promotes Colorectal Cancer Progression by the MicroRNA 149/HMGA2 Axis

    Colorectal cancer (CRC) has developed into the third leading cause of cancer-associated death worldwide. Studies have confirmed that circular RNAs (circRNAs) absorb microRNAs (miRNAs) to regulate the function of downstream genes.

    Kunpeng Liu, Yuhua Mou, Xiufang Shi, Tingkun Liu, Zhanfeng Chen, Xingmei Zuo
  • Sirtuin 5 Is Regulated by the SCF<sup>Cyclin F</sup> Ubiquitin Ligase and Is Involved in Cell Cycle Control
    Research Article | Spotlight
    Sirtuin 5 Is Regulated by the SCFCyclin F Ubiquitin Ligase and Is Involved in Cell Cycle Control

    The ubiquitin-proteasome system is essential for cell cycle progression. Cyclin F is a cell cycle-regulated substrate adapter F-box protein for the Skp1, CUL1, and F-box protein (SCF) family of E3 ubiquitin ligases.

    Christine A. Mills, Xianxi Wang, Dhaval P. Bhatt, Paul A. Grimsrud, Jacob Peter Matson, Debojyoti Lahiri, Daniel J. Burke, Jeanette Gowen Cook, Matthew D. Hirschey, Michael J. Emanuele
  • The N-Terminal Tail of Histone H3 Regulates Copper Homeostasis in <span class="named-content genus-species" id="named-content-1">Saccharomyces cerevisiae</span>
    Research Article
    The N-Terminal Tail of Histone H3 Regulates Copper Homeostasis in Saccharomyces cerevisiae

    Copper homeostasis is crucial for cellular processes. The balance between nutritional and toxic levels is maintained through the regulation of uptake, distribution, and detoxification via antagonistic actions of two transcription factors, AceI and Mac1.

    Sakshi Singh, Rakesh Kumar Sahu, Raghuvir Singh Tomar
  • STAT5 Regulation of Sex-Dependent Hepatic CpG Methylation at Distal Regulatory Elements Mapping to Sex-Biased Genes
    Research Article | Spotlight
    STAT5 Regulation of Sex-Dependent Hepatic CpG Methylation at Distal Regulatory Elements Mapping to Sex-Biased Genes

    Growth hormone-activated STAT5b is an essential regulator of sex-differential gene expression in mouse liver; however, its impact on hepatic gene expression and epigenetic responses is poorly understood. Here, we found a substantial, albeit incomplete loss of liver sex bias in hepatocyte-specific STAT5a/STAT5b (collectively, STAT5)-deficient mouse liver.

    Pengying Hao, David J. Waxman
  • Free
    Article of Significant Interest in This Issue
    Spotlight
    Article of Significant Interest in This Issue
  • Alternative Splicing and Cleavage of GLUT8
    Research Article
    Alternative Splicing and Cleavage of GLUT8

    The GLUT (SLC2) family of membrane-associated transporters are described as glucose transporters. However, this family is divided into three classes and, though the regulated transporter activity of class I proteins is becoming better understood, class III protein functions continue to be obscure. We have cataloged the relative expression and splicing of SLC2 mRNA isomers in tumors and normal tissues, with a focus on...

    Caroline M. Alexander, Joshua A. Martin, Elias Oxman, Ildiko Kasza, Katherine A. Senn, Heidi Dvinge
  • Analysis of 1,25-Dihydroxyvitamin D<sub>3</sub> Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids
    Research Article
    Analysis of 1,25-Dihydroxyvitamin D3 Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids

    Although vitamin D is critical for the function of the intestine, most studies have focused on the duodenum. We show that transgenic expression of the vitamin D receptor (VDR) only in the distal intestine of VDR null mice (KO/TG mice) results in the normalization of serum calcium and rescue of rickets. Although it had been suggested that calcium transport in the distal intestine involves a paracellular process, we found that the 1,25-...

    Shanshan Li, Jessica De La Cruz, Steven Hutchens, Somshuvra Mukhopadhyay, Zachary K. Criss, Rohit Aita, Oscar Pellon-Cardenas, Joseph Hur, Patricia Soteropoulos, Seema Husain, Puneet Dhawan, Lieve Verlinden, Geert Carmeliet, James C. Fleet, Noah F. Shroyer, Michael P. Verzi, Sylvia Christakos
  • Manipulation of Developmental Gamma-Globin Gene Expression: an Approach for Healing Hemoglobinopathies
    Minireview | Spotlight
    Manipulation of Developmental Gamma-Globin Gene Expression: an Approach for Healing Hemoglobinopathies

    β-Hemoglobinopathies are the most common monogenic disorders, and a century of research has provided us with a better understanding of the attributes of these diseases. Allogenic stem cell transplantation was the only potentially curative option available for these diseases until the discovery of gene therapy. The findings on the protective nature of fetal hemoglobin in sickle cell disease (SCD) and thalassemia patients carrying...

    Vigneshwaran Venkatesan, Saranya Srinivasan, Prathibha Babu, Saravanabhavan Thangavel

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