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Casein kinase 2

Beata Jonik-Nowak, Thomas Menneteau, Didier Fesquet, Véronique Baldin, Catherine Bonne-Andrea, Francisca Méchali, Bertrand Fabre, Prisca Boisguerin, Sylvain de Rossi, Corinne Henriquet, Martine Pugnière, Manuelle Ducoux-Petit, Odile Burlet-Schiltz, Angus I Lamond, Philippe Fort, Séverine Boulon, Marie-Pierre Bousquet, Olivier Coux
PA28γ is a nuclear activator of the 20S proteasome involved in the regulation of several essential cellular processes, such as cell proliferation, apoptosis, nuclear dynamics, and cellular stress response. Unlike the 19S regulator of the proteasome, which specifically recognizes ubiquitylated proteins, PA28γ promotes the degradation of several substrates by the proteasome in an ATP- and ubiquitin-independent manner. However, its exact mechanisms of action are unclear and likely involve additional partners that remain to be identified...
June 22, 2018: Proceedings of the National Academy of Sciences of the United States of America
Simone Di Micco, Luana Pulvirenti, Ines Bruno, Stefania Terracciano, Alessandra Russo, Maria C Vaccaro, Dafne Ruggiero, Vera Muccilli, Nunzio Cardullo, Corrado Tringali, Raffaele Riccio, Giuseppe Bifulco
The natural product magnolol (1) and a selection of its bioinspired derivatives 2-5, were investigated by Inverse Virtual Screening in order to identify putative biological targets from a panel of 308 proteins involved in cancer processes. By this in silico analysis we selected tankyrase-2 (TNKS2), casein kinase 2 (CK2) and bromodomain 9 (Brd9) as potential targets for experimental evaluations. The Surface Plasmon Resonance assay revealed that 3-5 present a good affinity for tankyrase-2, and, in particular, 3 showed an antiproliferative activity on A549 cells higher than the well-known tankyrase-2 inhibitor XAV939 used as reference compound...
June 20, 2018: Bioorganic & Medicinal Chemistry
Kentaro Furukawa, Tomoyuki Fukuda, Shun-Ichi Yamashita, Tetsu Saigusa, Yusuke Kurihara, Yutaka Yoshida, Hiromi Kirisako, Hitoshi Nakatogawa, Tomotake Kanki
Mitophagy plays an important role in mitochondrial quality control. In yeast, phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 (CK2) upon induction of mitophagy is a prerequisite for interaction of Atg32 with Atg11 (an adaptor protein for selective autophagy) and following delivery of mitochondria to the vacuole for degradation. Because CK2 is constitutively active, Atg32 phosphorylation must be precisely regulated to prevent unrequired mitophagy. We found that the PP2A (protein phosphatase 2A)-like protein phosphatase Ppg1 was essential for dephosphorylation of Atg32 and inhibited mitophagy...
June 19, 2018: Cell Reports
Mu Chen, Dechun Yin, Shuai Guo, Dong-Zhu Xu, Zhuo Wang, Zhenhui Chen, Michael Rubart-von der Lohe, Shien-Fong Lin, Thomas H Everett, James N Weiss, Peng-Sheng Chen
KEY POINTS: It is unknown if sex difference exists in cardiac apamin sensitive small conductance Ca2+ activated K+ (SK) current (IKAS ). There is no sex difference in IKAS at basal condition. However, there is larger IKAS in female rabbit ventricles than in males during isoproterenol infusion. IKAS activation by isoproterenol leads to action potential triangulation in females, indicating its abundant activation at early phases of repolarization. IKAS activation in females induces negative Ca2+ -voltage coupling and promotes electromechanical discordant phase 2 repolarization alternans...
June 19, 2018: Journal of Physiology
Emmanuelle Gouot, Wajid Bhat, Anne Rufiange, Eric Fournier, Eric Paquet, Amine Nourani
CK2 is an essential protein kinase implicated in various cellular processes. In this study, we address a potential role of this kinase in chromatin modulations associated with transcription. We found that CK2 depletion from yeast cells leads to replication-independent increase of histone H3K56 acetylation and global activation of H3 turnover in coding regions. This suggests a positive role of CK2 in maintenance/recycling of the histone H3/H4 tetramers during transcription. Interestingly, strand-specific RNA-seq analyses show that CK2 inhibits global cryptic promoters driving both sense and antisense transcription...
June 14, 2018: Nucleic Acids Research
Yasunori Fukumoto, Kazuaki Takahashi, Noriyuki Suzuki, Yasumitsu Ogra, Yuji Nakayama, Naoto Yamaguchi
An interaction between the Rad17-RFC2-5 and 9-1-1 complexes is essential for ATR-Chk1 signaling, which is one of the major DNA damage checkpoints. Recently, we showed that the polyanionic C-terminal tail of human Rad17 and the embedded conserved sequence iVERGE are important for the interaction with 9-1-1 complex. Here, we show that Rad17-S667 in the C-terminal tail is constitutively phosphorylated in vivo in a casein kinase 2-dependent manner, and the phosphorylation is important for 9-1-1 interaction. The serine phosphorylation of Rad17 could be seen in the absence of exogenous genotoxic stress, and was mostly abolished by S667A substitution...
June 11, 2018: Biochemical and Biophysical Research Communications
Roberto Magliozzi, Zunamys I Carrero, Teck Yew Low, Laurensia Yuniati, Christian Valdes-Quezada, Flore Kruiswijk, Koen van Wijk, Albert J R Heck, Catherine L Jackson, Daniele Guardavaccaro
Although much is known about how chromosome segregation is coupled to cell division, how intracellular organelles partition during mitotic division is poorly understood. We report that the phosphorylation-dependent degradation of the ARFGEF GBF1 regulates organelle trafficking during cell division. We show that, in mitosis, GBF1 is phosphorylated on Ser292 and Ser297 by casein kinase-2 allowing recognition by the F-box protein βTrCP. GBF1 interaction with βTrCP recruits GBF1 to the SCFβTrCP ubiquitin ligase complex, triggering its degradation...
June 12, 2018: Cell Reports
Yan-Yun Liu, Gregory A Brent
TR phosphorylation promotes TR binding to DNA and heterodimerization with RXR. TRβ phosphorylation is induced by thyroid hormone on the cell membrane and phosphorylation by extracellular signal-regulated kinases (ERK), presumably at serine 142. TRα1 N-termini harbors two phosphorylation sites at serine 12 and serine 28/29. Serine 12 is phosphorylated by casein 2 and serine 28/29 by protein kinase A. Mutation analysis of TRα2 identified 2 serine sites, S472 and S473, as the substrates for casein kinase II...
2018: Methods in Molecular Biology
Luiza M Bessa, Robert Schneider, Xavier Hanoulle
The Hepatitis C Virus (HCV) nonstructural 5A protein (NS5A) is a phosphoprotein (Evans et al., 2004; Ross-Thriepland and Harris, 2014) [1], [2] composed of an N-terminal well-structured domain and two C-terminal intrinsically disordered domains (Moradpour et al., 2007; Bartenschlager et al., 2013; Badillo et al., 2017) [3], [4], [5]. So far, no precise molecular function has been identified for this viral protein (Ross-Thriepland and Harris, 2015) [6] which is required for viral replication (Tellinghuisen et al...
April 2018: Data in Brief
Mingzhang Gao, Min Wang, Qi-Huang Zheng
The reference standards methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate (5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide (5c), and their corresponding desmethylated precursors 3-((2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoic acid (6a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4',5':4,5]benzo[1,2-d]imidazol-6-yl)-3-hydroxybenzamide (6b), were synthesized from 5-amino-2,2-difluoro-1,3-benzodioxole and 3-substituted benzoic acids in 5 and 6 steps with 33% and 11%, 30% and 7% overall chemical yield, respectively...
May 29, 2018: Bioorganic & Medicinal Chemistry Letters
Chu Chen, Guo-Feng Bao, Guanhua Xu, Yuyu Sun, Zhi-Ming Cui
Facet joint osteoarthritis is common lumbar osteoarthritis characterized by facet joint cartilage degeneration. However, the molecular basis of facet joint osteoarthritis remains largely undetermined. In the current study, we collected facet joint tissue samples from 10 control patients and 48 patients with facet joint osteoarthritis (20 patients with moderate degeneration and 28 with severe degeneration). The control patients underwent internal fixation of the lumbar spine due to vertebral fracture. RNA deep sequencing was performed, and Bioinformatic tools were applied...
2018: Tohoku Journal of Experimental Medicine
Yukari Nagatoshi, Miki Fujita, Yasunari Fujita
Our transient gene expression analyses in Arabidopsis protoplasts support the view that CK2αs and CK2βs positively and negatively modulate ABRE-dependent gene expression, respectively. The phytohormone abscisic acid (ABA) regulates the expression of thousands of genes via ABA-responsive elements (ABREs), and has a crucial role in abiotic stress response. Casein kinase II (CK2), a conserved Ser/Thr protein kinase in eukaryotes, is essential for plant viability. Although the CK2 has been known as a tetrameric holoenzyme comprised of two catalytic α and two regulatory β subunits, each of the two types of subunits has been proposed to have independent functions...
May 24, 2018: Planta
Rajesh Narasimamurthy, Sabrina R Hunt, Yining Lu, Jean-Michel Fustin, Hitoshi Okamura, Carrie L Partch, Daniel B Forger, Jae Kyoung Kim, David M Virshup
Multisite phosphorylation of the PERIOD 2 (PER2) protein is the key step that determines the period of the mammalian circadian clock. Previous studies concluded that an unidentified kinase is required to prime PER2 for subsequent phosphorylation by casein kinase 1 (CK1), an essential clock component that is conserved from algae to humans. These subsequent phosphorylations stabilize PER2, delay its degradation, and lengthen the period of the circadian clock. Here, we perform a comprehensive biochemical and biophysical analysis of mouse PER2 (mPER2) priming phosphorylation and demonstrate, surprisingly, that CK1δ/ε is indeed the priming kinase...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
Alexander Plotnikov, Dana Chuderland, Yael Karamansha, Oded Livnah, Rony Seger
No abstract text is available yet for this article.
June 1, 2018: Molecular and Cellular Biology
Qing Zhang, Yiyuan Xia, Yongjun Wang, Yangping Shentu, Kuan Zeng, Yacoubou A R Mahaman, Fang Huang, Mengjuan Wu, Dan Ke, Qun Wang, Bin Zhang, Rong Liu, Jian-Zhi Wang, Keqiang Ye, Xiaochuan Wang
Casein kinase 2 (CK2) is highly activated in Alzheimer disease (AD) and is associated with neurofibrillary tangles formation. Phosphorylated SET, a potent PP2A inhibitor, mediates tau hyperphosphorylation in AD. However, whether CK2 phosphorylates SET and regulates tau pathological phosphorylation in AD remains unclear. Here, we show that CK2 phosphorylating SET at Ser9 induced tau hyperphosphorylation in AD. We found that either Aβ treatment or tau overexpression stimulated CK2 activation leading to SET Ser9 hyperphosphorylation in neurons and animal models, while inhibition of CK2 by TBB abolished this event...
2018: Frontiers in Molecular Neuroscience
Feng-Ming Yang, Yong Zuo, Wei Zhou, Chuan Xia, Bumsuk Hahm, Mark Sullivan, Jinke Cheng, Hui-Ming Chang, Edward Th Yeh
Many Toll-like receptors (TLRs) signal through TNF receptor-associated factor 6 (TRAF6) to activate innate immune responses. Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways...
May 7, 2018: Journal of Clinical Investigation
Hiroko Maruyama, Fumitaka Kawakami, Thet-Thet Lwin, Motoki Imai, Fazel Shamsa
In this study, we examined the inhibitory effects of ferulic acid and caffeic acid on melanin production using a murine B16 melanoma cell line. The mechanisms by which the two acids inhibit melanin production were investigated by evaluating their effects on the activity of tyrosinase, which is involved is the first step of melanin biosynthesis. Ferulic acid showed no toxicity against the melanoma cells at any dose, whereas caffeic acid exerted cellular toxicity at concentrations higher than 0.35 mM. Both ferulic and caffeic acids effectively inhibited melanin production in the B16 melanoma cells...
2018: Biological & Pharmaceutical Bulletin
K S Suhas, Subhashree Parida, Chandrasekaran Gokul, Vivek Srivastava, E Prakash, Sakshi Chauhan, Thakur Uttam Singh, Manjit Panigrahi, Avinash G Telang, Santosh K Mishra
NEW FINDINGS: What is the central question of this study? Does the inhibition of the protein kinase casein kinase 2 (CK2) alter the uterine contractility? What is the main finding and its importance? Inhibition of CK2 impaired the spontaneous and oxytocin-induced contractility in late pregnant mouse uterus. This finding suggests that CK2 is a novel pathway mediating oxytocin-induced contractility in the uterus and thus opens up the possibility for this class of drugs to be developed as a new class of tocolytics...
May 1, 2018: Experimental Physiology
Abbas Kabir, Kalpana Tilekar, Neha Upadhyay, C S Ramaa
Background - Cancer being a complex disease, single targeting agents remains unsuccessful. This calls for "multiple targeting", wherein a single drug is so designed that it will modulate the activity of multiple protein targets. Topoisomerase 2 (Top2) helps in removing DNA tangles and super-coiling during cellular replication, Casein Kinase 2 (CK2) is involved in the phosphorylation of multitude of protein targets. Thus, in the present work, we have tried to develop dual inhibitors of Top2 and CK2...
April 22, 2018: Anti-cancer Agents in Medicinal Chemistry
X Peng, X Wu, J Zhang, G Zhang, G Li, X Pan
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, which results in increased bone fragility and fracture risk. Casein kinase 2-interacting protein-1 (CKIP-1) is a protein that plays an important role in regulation of bone formation. The effect of CKIP-1 on bone formation is mainly mediated through negative regulation of the bone morphogenetic protein pathway. In addition, CKIP-1 has an important role in the progression of osteoporosis...
February 2018: Bone & Joint Research
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