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Latest Articles

  • MicroRNA 27a Is a Key Modulator of Cholesterol Biosynthesis
    Research Article
    MicroRNA 27a Is a Key Modulator of Cholesterol Biosynthesis

    Hypercholesterolemia is a strong predictor of cardiovascular diseases. The 3-hydroxy-3-methylglutaryl coenzyme A reductase gene (Hmgcr) coding for the rate-limiting enzyme in the cholesterol biosynthesis pathway is a crucial regulator of plasma cholesterol levels. However, the posttranscriptional regulation of Hmgcr remains poorly understood. The main objective of this study was to explore the role of microRNAs (miRNAs) in the...

    Abrar A. Khan, Heena Agarwal, S. Santosh Reddy, Vikas Arige, Bhargavi Natarajan, Vinayak Gupta, Ananthamohan Kalyani, Manoj K. Barthwal, Nitish R. Mahapatra
  • TRAF2 Ser-11 Phosphorylation Promotes Cytosolic Translocation of the CD40 Complex To Regulate Downstream Signaling Pathways
    Research Article
    TRAF2 Ser-11 Phosphorylation Promotes Cytosolic Translocation of the CD40 Complex To Regulate Downstream Signaling Pathways

    CD40 plays an important role in immune responses by activating the c-Jun N-terminal protein kinase (JNK) and NF-κB pathways; however, the precise mechanisms governing the spatiotemporal activation of these two signaling pathways are not fully understood. Here, using four different TRAF2-deficient cell lines (A20.2J, CH12.LX, HAP1, and mouse embryonic fibroblasts [MEFs]) reconstituted with wild-type or phosphorylation mutant forms of...

    Lauren M. Workman, Laiqun Zhang, Yumei Fan, Weizhou Zhang, Hasem Habelhah
  • Mutual Balance of Histone Deacetylases 1 and 2 and the Acetyl Reader ATAD2 Regulates the Level of Acetylation of Histone H4 on Nascent Chromatin of Human Cells
    Research Article | Spotlight
    Mutual Balance of Histone Deacetylases 1 and 2 and the Acetyl Reader ATAD2 Regulates the Level of Acetylation of Histone H4 on Nascent Chromatin of Human Cells

    Newly synthesized histone H4 that is incorporated into chromatin during DNA replication is acetylated on lysines 5 and 12. Histone deacetylase 1 (HDAC1) and HDAC2 are responsible for reducing H4 acetylation as chromatin matures. Using CRISPR-Cas9-generated hdac1- or hdac2-null fibroblasts, we determined that HDAC1 and HDAC2 do not fully compensate for each other in removing de novo acetyls on H4 in vivo...

    Pavlo Lazarchuk, John Hernandez-Villanueva, Maria N. Pavlova, Alexander Federation, Michael MacCoss, Julia M. Sidorova
  • Free
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    Articles of Significant Interest in This Issue
  • Cell Cycle-Dependent Switch of TopBP1 Functions by Cdk2 and Akt
    Research Article
    Cell Cycle-Dependent Switch of TopBP1 Functions by Cdk2 and Akt

    Cdk2-dependent TopBP1-treslin interaction is critical for DNA replication initiation. However, it remains unclear how this association is terminated after replication initiation is finished. Here, we demonstrate that phosphorylation of TopBP1 by Akt coincides with cyclin A activation during S and G2 phases and switches the TopBP1-interacting partner from treslin to E2F1, which results in the termination of replication...

    Kang Liu, Joshua D. Graves, Yu-Ju Lee, Fang-Tsyr Lin, Weei-Chin Lin
  • Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity
    Research Article | Spotlight
    Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity

    Fibrosis is recognized as the major pathological change in adipose tissue during the development of obesity. However, the detailed mechanisms governing the interactions between the fibrotic components and their modifiers remain largely unclear. Here, we reported that matrix metalloproteinase 14 (MMP14), a key pericellular collagenase, is dramatically upregulated in obese adipose tissue. We generated a doxycycline-inducible adipose...

    Xin Li, Yueshui Zhao, Chuan Chen, Li Yang, Hyun-ho Lee, Zening Wang, Ningyan Zhang, Mikhail G. Kolonin, Zhiqiang An, Xin Ge, Philipp E. Scherer, Kai Sun
  • Therapeutic IDOL Reduction Ameliorates Amyloidosis and Improves Cognitive Function in APP/PS1 Mice
    Research Article | Spotlight
    Therapeutic IDOL Reduction Ameliorates Amyloidosis and Improves Cognitive Function in APP/PS1 Mice

    Brain lipoprotein receptors have been shown to regulate the metabolism of ApoE and β-amyloid (Aβ) and are potential therapeutic targets for Alzheimer’s disease (AD). Previously, we identified E3 ubiquitin ligase IDOL as a negative regulator of brain lipoprotein receptors. Genetic ablation of Idol increases low-density lipoprotein receptor protein levels, which facilitates Aβ uptake and clearance by microglia. In this study, we...

    Jie Gao, Russell Littman, Graciel Diamante, Xu Xiao, In Sook Ahn, Xia Yang, Tracy A. Cole, Peter Tontonoz
  • <em>Ipr1</em> Regulation by Cyclic GMP-AMP Synthase/Interferon Regulatory Factor 3 and Modulation of <em>Irgm1</em> Expression via <em>p53</em>
    Research Article
    Ipr1 Regulation by Cyclic GMP-AMP Synthase/Interferon Regulatory Factor 3 and Modulation of Irgm1 Expression via p53

    Intracellular pathogen resistance 1 (Ipr1) has been found to be a mediator to integrate cyclic GMP-AMP synthase (cGAS)–interferon regulatory factor 3 (IRF3), activated by intracellular pathogens, with the p53 pathway. Previous studies have shown the process of Ipr1 induction by various immune reactions, including intracellular bacterial and viral infections. The present study demonstrated that Ipr1 is...

    Fayang Liu, Hongni Xue, Jie Ke, Yongyan Wu, Kezhen Yao, Shuxin Liang, Aihua Xu, Yong Zhang
  • Meiosis-Specific Functions of Kinesin Motors in Cohesin Removal and Maintenance of Chromosome Integrity in Budding Yeast
    Research Article
    Meiosis-Specific Functions of Kinesin Motors in Cohesin Removal and Maintenance of Chromosome Integrity in Budding Yeast

    Kinesin motors provide the molecular forces at the kinetochore-microtubule interface and along the spindle to control chromosome segregation. During meiosis with two rounds of microtubule assembly-disassembly, the roles of motor proteins remain unexplored. We observed that in contrast to mitosis, Cin8 and Kip3 together are indispensable for meiosis. While examining meiosis in cin8Δ kip3Δ cells, we detected chromosome...

    Priyanka Mittal, Komal Ghule, Deepika Trakroo, Hemant Kumar Prajapati, Santanu K. Ghosh
  • Free
    Articles of Significant Interest in This Issue
    Spotlight
    Articles of Significant Interest in This Issue

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