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Allotypic variation in antigen processing controls antigenic peptide generation from SARS-CoV‐2 S1 Spike Glycoprotein

George Stamatakis, Martina Samiotaki, Ioannis Temponeras, George Panayotou, Efstratios Stratikos,

Population genetic variability in immune system genes can often underlie variability in immune responses to pathogens. Cytotoxic T-lymphocytes are emerging as critical determinants of both SARS-CoV-2 infection severity and long-term immunity, after either recovery or vaccination. A hallmark of COVID-19 is its highly variable severity and breadth of immune responses ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :]

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Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K/eNOS-dependent manner during inflammation

Jie Xiao, Ben Zhang, Zhengchen Su, Yakun Liu, Thomas R. Shelite, Qing Chang, Yuan Qiu, Jiani Bei, Pingyuan Wang, Alexander Bukreyev, Lynn Soong, Yang Jin, Thomas Ksiazek, Angelo Gaitas, Shannan L. Rossi, Jia Zhou, Michael Laposata, Tais B. Saito, Bin Gong,

Coagulopathy is associated with both inflammation and infection, including infection with novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. Clot formation is promoted via cyclic adenosine monophosphate (cAMP)-mediated secretion of von Willebrand factor (vWF), which fine tunes the process of hemostasis. The exchange protein directly activated ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :]

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Human CEACAM1-LF regulates lipid storage in HepG2 cells via fatty acid transporter CD36.

Jennifer Chean, Charng-Jui Chen, Gabriel Gugiu, Patty Wong, Seung Cha, Harry Li, Tung Nguyen, Supriyo Bhatticharya, John E Shively,

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in liver and secreted as biliary glycoprotein 1 (BGP1) via bile canaliculi (BCs). CEACAM1-LF is a 72 amino acid cytoplasmic domain mRNA splice isoform with two immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Ceacam1-/- or Ser503Ala transgenic mice have been shown to develop ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101311]

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Phosphorylation of human CEACAM1-LF by PKA and GSK3β promote its interaction with β-catenin.

Weidong Hu, Karine Bagramyan, Supriyo Bhatticharya, Teresa Hong, Alonso Tapia, Patty Wong, Markus Kalkum, John E Shively,

CEACAM1-LF, a homotypic cell adhesion adhesion molecule, transduces intracellular signals via a 72 amino acid cytoplasmic domain that contains two immunoreceptor tyrosine based inhibitory motifs (ITIMs) and a binding site for β-catenin. Phosphorylation of Ser503 by PKC in rodent CEACAM1 was shown to affect bile acid transport or hepatosteatosis via ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101305]

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Phosphoinositide binding activity of Smad2 is essential for its function in TGF-β signaling.

Pawanthi Buwaneka, Arthur Ralko, Sukhamoy Gorai, Ha Pham, Wonhwa Cho,

As a central player in the canonical TGF-β signaling pathway, Smad2 transmits the activation of TGF-β receptors at the plasma membrane (PM) to transcriptional regulation in the nucleus. Although it has been well established that binding of TGF-β to its receptors leads to the recruitment and activation of Smad2, the ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101303]

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Structural and thermodynamical insights into the binding and inhibition of FIH-1 by the N-terminal disordered region of Mint3.

Tensho Ten, Satoru Nagatoishi, Ryo Maeda, Masaru Hoshino, Yoshiaki Nakayama, Motoharu Seiki, Takeharu Sakamoto, Kouhei Tsumoto,

Mint3 is known to enhance aerobic ATP production, known as the Warburg effect, by binding to FIH-1. Since this effect is considered to be beneficial for cancer cells, the interaction is a promising target for cancer therapy. However, previous research has suggested that the interacting region of Mint3 with FIH-1 ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101304]

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The ephrin receptor EphB2 regulates the connectivity and activity of enteric neurons.

Raphael Bodin, Vincent Paille, Thibauld Oullier, Tony Durand, Philippe Aubert, Catherine Le Berre-Scoul, Philippe Hulin, Michel Neunlist, Moustapha Cisse,

Highly organized circuits of enteric neurons are required for the regulation of gastrointestinal functions, such as peristaltism or migrating motor complex. However, the factors and molecular mechanisms that regulate the connectivity of enteric neurons and their assembly into functional neuronal networks are largely unknown. A better understanding of the mechanisms ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101300]

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Neddylation modification of the U3 snoRNA binding protein RRP9 by Smurf1 promotes tumorigenesis.

Meng-Ge Du, Fan Liu, Yan Chang, Shuai Tong, Wei Liu, Yu-Jiao Chen, Ping Xie,

Neddylation is a post-translational modification that attaches ubiquitin-like protein Nedd8 to protein targets via Nedd8-specific E1-E2-E3 enzymes, and modulates many important biological processes. Nedd8 attaches to a lysine residue of a substrate, not for degradation, but for modulation of substrate activity. We previously identified the HECT-type ubiquitin ligase Smurf1, which ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101307]

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Correction: A conserved strategy for structure change and energy transduction in Hsp104 and other AAA+ protein motors.

Xiang Ye, Leland Mayne, S Walter Englander,

J Biol Chem (The Journal of biological chemistry)
[2021, 297(5):101285]

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Flipping the switch: how cysteine oxidation directs tau amyloid conformations.

Danny M Hatters,

Tau can adopt distinct fibril conformations in different human neurodegenerative diseases which may invoke distinct pathological mechanisms. In a recent issue, Weismiller et al showed that intramolecular disulfide links between cys291 and cys322 for a specific tau isoform containing 4 microtubule-binding repeats direct the formation of a structurally distinct amyloid ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101309]

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Tryptophan (W) at position 37 of murine IL-12/IL-23 p40 is mandatory for binding to IL-12Rβ1 and subsequent signal transduction.

Jacqueline Georgy, Yvonne Arlt, Jens M Moll, Meryem Ouzin, Hendrik T Weitz, Lothar Gremer, Dieter Willbold, Joachim Grötzinger, Felix Thives-Kurenbach, Jürgen Scheller, Doreen M Floss,

Interleukin (IL)-12 and IL-23 are composite cytokines consisting of p35/p40 and p19/p40, respectively, which signal via the common IL-12 receptor β1 (IL-12Rβ1) and the cytokine-specific receptors IL-12Rβ2 and IL-23R. Previous data showed that the p40 component interacts with IL-12Rβ1, whereas p19 and p35 subunits solely bind to IL-23R and IL-12Rβ2, ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101295]

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The Sigma-1 receptor is an ER-localized type II membrane protein.

Neeraj Sharma, Chaitanya Patel, Marina Shenkman, Amit Kessel, Nir Ben-Tal, Gerardo Z Lederkremer,

The Sigma-1 receptor (S1R) is a transmembrane protein with important roles in cellular homeostasis in normal physiology and in disease. Especially in neurodegenerative diseases, S1R activation has been shown to provide neuroprotection by modulating calcium signaling, mitochondrial function and reducing endoplasmic reticulum (ER) stress. S1R missense mutations are one of ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101299]

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Cardiac myosin contraction and mechanotransduction in health and disease.

Samantha K Barrick, Michael J Greenberg,

Cardiac myosin is the molecular motor that powers heart contraction by converting chemical energy from ATP hydrolysis into mechanical force. The power output of the heart is tightly regulated to meet the physiological needs of the body. Recent multiscale studies spanning from molecules to tissues have revealed complex regulatory mechanisms ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101297]

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Tyrosine Phosphorylation of DEPTOR Functions as a Molecular Switch to Activate mTOR Signaling.

Laurence M Gagné, Nadine Morin, Noémie Lavoie, Nicolas Bisson, Jean-Philippe Lambert, Frédérick A Mallette, Marc-Étienne Huot,

Metabolic dysfunction is a major driver of tumorigenesis. The serine/threonine kinase mTOR constitutes a key central regulator of metabolic pathways promoting cancer cell proliferation and survival. mTOR activity is regulated by metabolic sensors as well as by numerous factors comprising the PTEN/PI3K/AKT canonical pathway, which are often mutated in cancer. ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101291]

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Basolateral protein Scribble binds phosphatase PP1 to establish a signaling network maintaining apicobasal polarity.

Regina B Troyanovsky, Indrajyoti Indra, Rei Kato, Brian J Mitchell, Sergey M Troyanovsky,

Scribble, a member of the LAP protein family, contributes to the apicobasal polarity (ABP) of epithelial cells. The LAP-unique region of these proteins, which is essential and sufficient for ABP, includes a conserved Leucine-Rich Repeat (LRR) domain. The major binding partners of this region that could regulate ABP remain unknown. ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101289]

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Impaired beta-oxidation increases vulnerability to Influenza A infection.

Sebastiaan van Liempd, Diana Cabrera, Carolin Pilzner, Heike Kollmus, Klaus Schughart, Juan M Falcón-Pérez,

Influenza A virus (IAV) infection casts a significant burden on society. It has particularly high morbidity and mortality rates in patients suffering from metabolic disorders. The aim of this study was to relate metabolic changes with IAV susceptibility using well-characterized, inbred mouse models. We compared the highly susceptible DBA/2J (D2) ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101298]

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Phylogenetic analysis and in-depth characterization of functionally and structurally diverse CE5 cutinases.

Vera Novy, Leonor Vieira Carneiro, Jae Ho Shin, Johan Larsbrink, Lisbeth Olsson,

Cutinases are esterases that release fatty acids from the apoplastic layer in plants. As they accept bulky and hydrophobic substrates, cutinases could be used in many applications, ranging from valorization of bark-rich side streams to plastic recycling. Advancement of these applications with cutinases as biocatalysts, however, requires deeper knowledge of ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101302]

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The ion channel TRPM7 regulates zinc depletion-induced MDMX degradation.

Herui Wang, Bin Li, Kulsum Asha, Ryan L Pangilinan, Asha Thuraisamy, Harman Chopra, Susumu Rokudai, Yong Yu, Carol L Prives, Yan Zhu,

Zinc deficiency has been linked to human diseases, including cancer. MDMX, a crucial zinc-containing negative regulator of p53, has been found to be amplified or overexpressed in various cancers and implicated in the cancer initiation and progression. We report here that zinc depletion by the ion chelator TPEN or Chelex ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101292]

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Sulfation of glycosaminoglycans depends on catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro.

Brynna S Eisele, Zigmund Luka, Alice J Wu, Fei Yang, Andrew T Hale, John D York,

Golgi-resident bisphosphate nucleotidase 2 (BPNT2) is a member of a family of magnesium-dependent, lithium-inhibited phosphatases that share a three-dimensional structural motif that directly coordinates metal binding to effect phosphate hydrolysis. BPNT2 catalyzes the breakdown of 3'-phosphoadenosine-5'-phosphate (PAP), a by-product of glycosaminoglycan (GAG) sulfation. Knockout of BPNT2 in mice leads to ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101293]

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Lamin-A/C recruits ssDNA protective proteins RPA and RAD51 to stalled replication forks to maintain fork stability.

Simona Graziano, Nuria Coll-Bonfill, Barbara Teodoro-Castro, Sahiti Kuppa, Jessica Jackson, Elena Shashkova, Urvashi Mahajan, Alessandro Vindigni, Edwin Antony, Susana Gonzalo,

Lamin-A/C provides a nuclear scaffold for compartmentalization of genome function that is important for genome integrity. Lamin-A/C dysfunction is associated with cancer, aging, and degenerative diseases. The mechanisms whereby lamin-A/C regulates genome stability remain poorly understood. We demonstrate a crucial role for lamin-A/C in DNA replication. We show that lamin-A/C ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101301]

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Emerging roles of epigenetic regulation in obesity and metabolic disease.

Yoon Jeong Park, Sang Mun Han, Jin Young Huh, Jae Bum Kim,

Adipose tissue dysfunction is a hallmark of obesity and contributes to obesity-related sequelae such as metabolic complications and insulin resistance. Compelling evidence indicates that adipose tissue-specific gene expression is influenced by gene interactions with proximal and distal cis-regulatory elements; the latter exert regulatory effects via three-dimensional (3D) chromosome conformation. Recent ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101296]

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Metabolic turnover and dynamics of modified ribonucleosides by 13C labeling.

Paulo A Gameiro, Vesela Encheva, Mariana Silva Dos Santos, James I MacRae, Jernej Ule,

Tandem mass spectrometry (MS/MS) is an accurate tool to assess modified ribonucleosides and their dynamics in mammalian cells. However, MS/MS quantification of lowly abundant modifications in non-ribosomal RNAs is unreliable, and the dynamic features of various modifications poorly understood. Here, we developed a <sup>13</sup>C labeling approach, called <sup>13</sup>C-dynamods, to quantify ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101294]

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ALS-Linked FUS mutations dysregulate G-quadruplex-dependent liquid-liquid phase separation and liquid-to-solid transition.

Akira Ishiguro, Jun Lu, Daisaku Ozawa, Yoshitaka Nagai, Akira Ishihama,

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the accumulation of protein aggregates in motor neurons. Recent discoveries of genetic mutations in ALS patients promoted research into the complex molecular mechanisms underlying ALS. FUS (fused in sarcoma) is a representative ALS-linked RNA-binding protein (RBP) that specifically recognizes G-quadruplex ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101284]

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Correction: Potentiation of tumor necrosis factor-α-induced tumor cell apoptosis by a small molecule inhibitor for anti-apoptotic protein hPEBP4.

Jianming Qiu, Jianfeng Xiao, Chaofeng Han, Nan Li, Xu Shen, Hualiang Jiang, Xuetao Cao,

J Biol Chem (The Journal of biological chemistry)
[2021, 297(4):101261]

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Labeling and Measuring Stressed Mitochondria Using a PINK1-Based Ratiometric Fluorescent Sensor.

Rie Uesugi, Shunsuke Ishii, Akira Matsuura, Eisuke Itakura,

Mitochondria are essential organelles that carry out a number of pivotal metabolic processes and maintain cellular homeostasis. Mitochondrial dysfunction caused by various stresses is associated with many diseases such as type 2 diabetes, obesity, cancer, heart failure, neurodegenerative disorders, and aging. Therefore, it is important to understand the stimuli that ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2021, :101279]

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