Read by QxMD icon Read

Ck1 delta

Surya Pratap Singh, Dwijendra K Gupta
Wnt signaling pathway regulates several developmental processes in human; however recently this pathway has been associated with development of different types of cancers. Casein kinase-1 (CK1) constitutes a family of serine-threonine protein kinase; various members of this family participate in Wnt signal transduction pathway and serve as molecular switch to this pathway. Among the known six isoforms of CK1, in human, at least three isoforms (viz. alpha, delta and epsilon) have been reported as oncogenic. The development of common therapeutics against these kinases is an arduous task; unless we have the detailed information of their tertiary structures and conformational properties...
April 21, 2015: Journal of Theoretical Biology
Filip Laco, Joo-Leng Low, Jasmin Seow, Tsung Liang Woo, Qixing Zhong, Jayasree Seayad, Zhenfeng Liu, Heiming Wei, Shaul Reuveny, David A Elliott, Christina L L Chai, Steve K W Oh
Differentiation of human pluripotent stem cells as embryoid bodies (EBs) has been achieved previously with p38alfa MAPK inhibitors such as SB203580 with moderate efficiency of 10-15%. We synthesized and screened 42 compounds that are 2,4,5-trisubstituted azole analogues of SB203580 for efficient cardiomyocyte differentiation. Our screen identified novel compounds that have similar cardiac differentiation activity as SB203580. However, the cardiac differentiation did not correlate with p38alfa MAPK inhibition, indicating an alternative mechanism in cardiac differentiation...
March 2015: Journal of Molecular and Cellular Cardiology
Travis T Wager, Ramalakshmi Y Chandrasekaran, Jenifer Bradley, David Rubitski, Helen Berke, Scot Mente, Todd Butler, Angela Doran, Cheng Chang, Katherine Fisher, John Knafels, Shenping Liu, Jeff Ohren, Michael Marconi, George DeMarco, Blossom Sneed, Kevin Walton, David Horton, Amy Rosado, Andy Mead
Casein kinase 1 delta (CK1δ) and casein kinase 1 epsilon (CK1ε) inhibitors are potential therapeutic agents for a range of psychiatric disorders. The feasibility of developing a CNS kinase inhibitor has been limited by an inability to identify safe brain-penetrant compounds with high kinome selectivity. Guided by structure-based drug design, potent and selective CK1δ/ε inhibitors have now been identified that address this gap, through the design and synthesis of novel 4-[4-(4-fluorophenyl)-1-(piperidin-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine derivatives...
December 17, 2014: ACS Chemical Neuroscience
Yoshimi Endo Greer, Christopher J Westlake, Bo Gao, Kapil Bharti, Yoko Shiba, Charles P Xavier, Gregory J Pazour, Yingzi Yang, Jeffrey S Rubin
Inhibition of casein kinase 1 delta (CK1δ) blocks primary ciliogenesis in human telomerase reverse transcriptase immortalized retinal pigmented epithelial and mouse inner medullary collecting duct cells-3. Mouse embryonic fibroblasts (MEFs) and retinal cells from Csnk1d (CK1δ)-null mice also exhibit ciliogenesis defects. CK1δ catalytic activity and centrosomal localization signal (CLS) are required to rescue cilia formation in MEFs(Csnk1d null). Furthermore, expression of a truncated derivative containing the CLS displaces full-length CK1δ from the centrosome and decreases ciliary length in control MEFs, suggesting that centrosomal CK1δ has a role in ciliogenesis...
May 2014: Molecular Biology of the Cell
Shu-Hui Lin, Yueh-Min Lin, Chung-Min Yeh, Chih-Jung Chen, Mei-Wen Chen, Hsiao-Fang Hung, Kun-Tu Yeh, Shun-Fa Yang
Casein kinase 1 is a group of ubiquitous serine/threonine kinases that are involved in normal cellular functions and several pathological conditions, such as DNA repair, cell cycle progression, cytokinesis, differentiation, and apoptosis. Recent studies have indicated that casein kinase 1-epsilon (CK1ε) and casein kinase 1-delta (CK1δ) expression has a role in human cancers. We investigated the associations between CK1ε and CK1δ expression and the clinical parameters of oral cancer using immunohistochemical study methods on oral squamous cell carcinoma specimens...
2014: International Journal of Molecular Sciences
Ambuj Kumar, Vidya Rajendran, Rao Sethumadhavan, Rituraj Purohit
CK1δ (Casein kinase I isoform delta) is a member of CK1 kinase family protein that mediates neurite outgrowth and the function as brain-specific microtubule-associated protein. ATP binding kinase domain of CK1δ is essential for regulating several key cell cycle signal transduction pathways. Mutation in CK1δ protein is reported to cause cancers and affects normal brain development. S97C mutation in kinase domain of CK1δ protein has been involved to induce breast cancer and ductal carcinoma. We performed molecular docking studies to examine the effect of this mutation on its ATP-binding affinity...
2014: Journal of Biomolecular Structure & Dynamics
Sima Smadja Storz, Adi Tovin, Philipp Mracek, Shahar Alon, Nicholas S Foulkes, Yoav Gothilf
Zebrafish have become a popular model for studies of the circadian timing mechanism. Taking advantage of its rapid development of a functional circadian clock and the availability of light-entrainable clock-containing cell lines, much knowledge has been gained about the circadian clock system in this species. However, the post-translational modifications of clock proteins, and in particular the phosphorylation of PER proteins by Casein kinase I delta and epsilon (CK1δ and CK1ε), have so far not been examined in the zebrafish...
2013: PloS One
Hao Chen, Honghui Ma, Hiroyuki Inuzuka, Jianbo Diao, Fei Lan, Yujiang Geno Shi, Wenyi Wei, Yang Shi
UHRF1 (ubiquitin-like, with PHD and RING finger domains 1) is a critical epigenetic player involved in the maintenance of DNA methylation patterns during DNA replication. Dysregulation of the UHRF1 level is implicated in cancer onset, metastasis, and tumor recurrence. Previous studies demonstrated that UHRF1 can be stabilized through USP7-mediated deubiquitylation, but the mechanism through which UHRF1 is ubiquitylated is still unknown. Here we show that proteasomal degradation of UHRF1 is mediated by the SCF(β-TrCP) E3 ligase...
March 2013: Molecular and Cellular Biology
Lorna S Kategaya, Aisha Hilliard, Louying Zhang, John M Asara, Louis J Ptáček, Ying-Hui Fu
Throughout the day, clock proteins synchronize changes in animal physiology (e.g., wakefulness and appetite) with external cues (e.g., daylight and food). In vertebrates, both casein kinase 1 delta and epsilon (CK1δ and CK1ε) regulate these circadian changes by phosphorylating other core clock proteins. In addition, CK1 can regulate circadian-dependent transcription in a non-catalytic manner, however, the mechanism is unknown. Furthermore, the extent of functional redundancy between these closely related kinases is debated...
2012: PloS One
Heidrun Hirner, Cagatay Günes, Joachim Bischof, Sonja Wolff, Arnhild Grothey, Marion Kühl, Franz Oswald, Florian Wegwitz, Michael R Bösl, Anna Trauzold, Doris Henne-Bruns, Christian Peifer, Frank Leithäuser, Wolfgang Deppert, Uwe Knippschild
Simian virus 40 (SV40) is a powerful tool to study cellular transformation in vitro, as well as tumor development and progression in vivo. Various cellular kinases, among them members of the CK1 family, play an important role in modulating the transforming activity of SV40, including the transforming activity of T-Ag, the major transforming protein of SV40, itself. Here we characterized the effects of mutant CK1δ variants with impaired kinase activity on SV40-induced cell transformation in vitro, and on SV40-induced mammary carcinogenesis in vivo in a transgenic/bi-transgenic mouse model...
2012: PloS One
Alexander Long, Huilin Zhao, Xin Huang
Casein kinase 1 delta (CK1δ) and its closest homologue CK1ε are key regulators of diverse cellular growth and survival processes such as Wnt signaling, DNA repair, and circadian rhythms. We report three crystal structures of the kinase domain of human CK1δ, one apo and two complexed with a potent and selective CK1δ/ε inhibitor PF670462 in two different crystal forms. These structures provide a molecular basis for the strong and specific inhibitor interactions and suggest clues for further development of CK1δ/ε inhibitors...
January 26, 2012: Journal of Medicinal Chemistry
Yoshimi Endo Greer, Jeffrey S Rubin
Previously we determined that Dishevelled-2/3 (Dvl) mediate Wnt-3a-dependent neurite outgrowth in Ewing sarcoma family tumor cells. Here we report that neurite extension was associated with Dvl phosphorylation and that both were inhibited by the casein kinase 1 (CK1) δ/ε inhibitor IC261. Small interfering RNAs targeting either CK1δ or CK1ε decreased Dvl phosphorylation, but only knockdown of CK1δ blocked neurite outgrowth. CK1δ but not CK1ε was detected at the centrosome, an organelle associated with neurite formation...
March 21, 2011: Journal of Cell Biology
J K Cheong, T H Nguyen, H Wang, P Tan, P M Voorhoeve, S H Lee, D M Virshup
Casein kinase 1 delta and epsilon (CK1δ/ɛ) are key regulators of diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. Recent studies suggest that they have an important role in oncogenesis. RNA interference screens identified CK1ɛ as a pro-survival factor in cancer cells in vitro and the CK1δ/ɛ-specific inhibitor IC261 is remarkably effective at selective, synthetic lethal killing of cancer cells. The recent development of the nanomolar CK1δ/ɛ-selective inhibitor, PF670462 (PF670) and the CK1ɛ-selective inhibitor PF4800567 (PF480) offers an opportunity to further test the role of CK1δ/ɛ in cancer...
June 2, 2011: Oncogene
Qing-Jun Meng, Elizabeth S Maywood, David A Bechtold, Wei-Qun Lu, Jian Li, Julie E Gibbs, Sandrine M Dupré, Johanna E Chesham, Francis Rajamohan, John Knafels, Blossom Sneed, Laura E Zawadzke, Jeffrey F Ohren, Kevin M Walton, Travis T Wager, Michael H Hastings, Andrew S I Loudon
Circadian pacemaking requires the orderly synthesis, posttranslational modification, and degradation of clock proteins. In mammals, mutations in casein kinase 1 (CK1) epsilon or delta can alter the circadian period, but the particular functions of the WT isoforms within the pacemaker remain unclear. We selectively targeted WT CK1epsilon and CK1delta using pharmacological inhibitors (PF-4800567 and PF-670462, respectively) alongside genetic knockout and knockdown to reveal that CK1 activity is essential to molecular pacemaking...
August 24, 2010: Proceedings of the National Academy of Sciences of the United States of America
Cornelia Rumpf, Lubos Cipak, Andrej Dudas, Zsigmond Benko, Miroslava Pozgajova, Christian G Riedel, Gustav Ammerer, Karl Mechtler, Juraj Gregan
Segregation of chromosomes during meiosis depends on separase cleavage of Rec8, the meiosis-specific alpha-kleisin subunit of cohesin. We mapped Rec8 phosphorylation sites by mass spectrometry and show that Rec8 phosphorylation is required for proper chromosome disjunction during meiosis. We further show that the fission yeast casein kinase 1 (CK1) delta/epsilon isoforms Hhp1 and Hhp2 are required for full levels of Rec8 phosphorylation and for efficient removal of Rec8 at the onset of anaphase I. Our data are consistent with the model that Hhp1/Hhp2-dependent phosphorylation of Rec8 is required for separase-mediated cleavage of Rec8 during meiosis I...
July 1, 2010: Cell Cycle
Andrea Venerando, Oriano Marin, Giorgio Cozza, Victor H Bustos, Stefania Sarno, Lorenzo Alberto Pinna
The ability of three isoforms of protein kinase CK1 (alpha, gamma(1), and delta) to phosphorylate the N-terminal region of p53 has been assessed using either recombinant p53 or a synthetic peptide reproducing its 1-28 sequence. Both substrates are readily phosphoylated by CK1delta and CK1alpha, but not by the gamma isoform. Affinity of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (K (m) 0.82 muM vs 1.51 mM). The preferred target is S20, whose phosphorylation critically relies on E17, while S6 is unaffected despite displaying the same consensus (E-x-x-S)...
April 2010: Cellular and Molecular Life Sciences: CMLS
Eri Sakurai, Takashi Kurihara, Kasumi Kouchi, Hironao Saegusa, Shuqin Zong, Tsutomu Tanabe
BACKGROUND: Neuropathic pain is a complex chronic pain generated by damage to, or pathological changes in the somatosensory nervous system. Characteristic features of neuropathic pain are allodynia, hyperalgesia and spontaneous pain. Such abnormalities associated with neuropathic pain state remain to be a significant clinical problem. However, the neuronal mechanisms underlying the pathogenesis of neuropathic pain are complex and still poorly understood. Casein kinase 1 is a serine/threonine protein kinase and has been implicated in a wide range of signaling activities such as cell differentiation, proliferation, apoptosis, circadian rhythms and membrane transport...
2009: Molecular Pain
Giorgio Cozza, Alessandra Gianoncelli, Monica Montopoli, Laura Caparrotta, Andrea Venerando, Flavio Meggio, Lorenzo A Pinna, Giuseppe Zagotto, Stefano Moro
In eukaryotes, protein phosphorylation of serine, threonine or tyrosine residues by protein kinases plays an important role in many cellular processes. Members of the protein kinase CK1 family usually phosphorylate residues of serine that are close to other phosphoserine in a consensus motif of pS-X-X-S, and they are implicated in the regulation of a variety of physiological processes as well as in pathologies like cancer and Alzheimer's disease. Using a structure-based virtual screening (SBVS) approach we have identified two anthraquinones as novel CK1delta inhibitors...
October 15, 2008: Bioorganic & Medicinal Chemistry Letters
Ali M Al-Housseini, Thamil Mani Sivanandam, Edward L Bradbury, Rudi K Tannenberg, Peter R Dodd, Qiang Gu
BACKGROUND: Chronic and excessive alcohol misuse results in neuroadaptive changes in the brain. The complex nature of behavioral, psychological, emotional, and neuropathological characteristics associated with alcoholism is likely a reflection of the network of proteins that are affected by alcohol-induced gene expression patterns in specific brain regions. At the molecular level, however, knowledge remains limited regarding alterations in protein expression levels affected by chronic alcohol abuse...
June 2008: Alcoholism, Clinical and Experimental Research
Fumitaka Kawakami, Kanzo Suzuki, Kenzo Ohtsuki
A novel phosphorylation motif for casein kinase 1 (CK1) in response to two sulfated lipids [sulfatide and cholesterol-3-sulfate (SCS)] was determined, using three functional proteins [myelin basic protein (MBP), tau protein (TP) and RhoA (a small GTPase)] and five synthetic MBP peptides as phosphate acceptors for the kinase in vitro. It was found that (i) MBP, p8 (positions 38-118) cleaved from MBP, and a synthetic peptide M103 were effectively phosphorylated by CK1delta in the presence of SCS; (ii) sulfatide in comparison with CH-3S highly enhanced autophosphorylation of CK1delta; (iii) SCS had a high binding affinity with MBP and peptide M103, but not other MBP peptides lacking K-G-R; and (iv) a novel consensus phosphorylation motif (K/R-X-K/R-X-X-S/T) for CK1 was identified among several SCS-binding proteins (SCS-BPs) and three CK1 isoforms (delta, epsilon and gamma)...
February 2008: Biological & Pharmaceutical Bulletin
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"