scholarly journals Evidence for Regulation of Mitotic Progression through Temporal Phosphorylation and Dephosphorylation of CK2α

2009 ◽  
Vol 29 (8) ◽  
pp. 2068-2081 ◽  
Author(s):  
Nicole A. St-Denis ◽  
D. Richard Derksen ◽  
David W. Litchfield
Keyword(s):  
Protein Kinase Ck2 ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Catastrophe ◽  
Mitotic Progression ◽  
Proliferating Cells ◽  
Cultured Fibroblasts ◽  
Catalytic Subunits ◽  
Chromosomal Segregation ◽  
Mitotic Phosphorylation ◽  
Kinase Ck2

ABSTRACT Proper mitotic progression is crucial for maintenance of genomic integrity in proliferating cells and is regulated through an intricate series of events, including protein phosphorylation governed by a complex network of protein kinases. One kinase family implicated in the regulation of mitotic progression is protein kinase CK2, a small family of enzymes that is overexpressed in cancer and induces transformation in mice and cultured fibroblasts. CK2α, one isoform of the catalytic subunits of CK2, is maximally phosphorylated at four sites in nocodazole-treated cells. To investigate the effects of CK2α phosphorylation on mitotic progression, we generated phosphospecific antibodies against its mitotic phosphorylation sites. In U2OS cells released from S-phase arrest, these antibodies reveal that CK2α is most highly phosphorylated in prophase and metaphase. Phosphorylation gradually decreases during anaphase and becomes undetectable during telophase and cytokinesis. Stable expression of phosphomimetic CK2α (CK2α-4D, CK2α-4E) results in aberrant centrosome amplification and chromosomal segregation defects and loss of mitotic cells through mitotic catastrophe. Conversely, cells expressing nonphosphorylatable CK2α (CK2α-4A) show a decreased ability to arrest in mitosis following nocodazole treatment, suggesting involvement in the spindle assembly checkpoint. Collectively, these studies indicate that reversible phosphorylation of CK2α requires precise regulation to allow proper mitotic progression.

Phosphorylation of thymidylate synthase from various sources by human protein kinase CK2 and its catalytic subunits

2010 ◽  
Vol 38 (3) ◽  
pp. 124-131 ◽  
Author(s):  
Tomasz Frączyk ◽  
Konrad Kubiński ◽  
Maciej Masłyk ◽  
Joanna Cieśla ◽  
Ulf Hellman ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Thymidylate Synthase ◽  
Protein Kinase Ck2 ◽  
Human Protein ◽  
Catalytic Subunits ◽  
Human Protein Kinase ◽  
Kinase Ck2

scholarly journals Uncoupling Anaphase-Promoting Complex/Cyclosome Activity from Spindle Assembly Checkpoint Control by Deregulating Polo-Like Kinase 1

2005 ◽  
Vol 25 (5) ◽  
pp. 2031-2044 ◽  
Author(s):  
Barbara C. M. van de Weerdt ◽  
Marcel A. T. M. van Vugt ◽  
Catherine Lindon ◽  
Jos J. W. Kauw ◽  
Marieke J. Rozendaal ◽  
...  
Keyword(s):  
Double Mutant ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Catastrophe ◽  
Anaphase Promoting Complex ◽  
Checkpoint Control ◽  
Mitotic Progression ◽  
Specific Antibodies ◽  
Mitotic Entry

ABSTRACT Polo-like kinase 1 (Plk1) plays a role in numerous events in mitosis, but how the multiple functions of Plk1 are separated is poorly understood. We studied regulation of Plk1 through two putative phosphorylation residues, Ser-137 and Thr-210. Using phospho-specific antibodies, we found that Thr-210 phosphorylation precedes Ser-137 phosphorylation in vivo, the latter occurring specifically in late mitosis. We show that expression of two activating mutants of these residues, S137D and T210D, results in distinct mitotic phenotypes. Whereas expression of both phospho-mimicking mutants as well as of the double mutant leads to accelerated mitotic entry, further progression through mitosis is dramatically different: the T210D mutant causes a spindle assembly checkpoint-dependent delay, whereas the expression of the S137D mutant or the double mutant results in untimely activation of the anaphase-promoting complex/cyclosome (APC/C) and frequent mitotic catastrophe. Using nonphosphorylatable Plk1-S137A and Plk1-T210A mutants, we show that both sites contribute to proper mitotic progression. Based on these observations, we propose that Plk1 function is altered at different stages of mitosis through consecutive posttranslational events, e.g., at Ser-137 and Thr-210. Furthermore, our data show that uncontrolled Plk1 activation can uncouple APC/C activity from spindle assembly checkpoint control.

scholarly journals Mitotic Phosphorylation of DNA Topoisomerase II α by Protein Kinase CK2 Creates the MPM-2 Phosphoepitope on Ser-1469

2000 ◽  
Vol 275 (44) ◽  
pp. 34710-34718 ◽  
Author(s):  
Alexandre E. Escargueil ◽  
Sergei Y. Plisov ◽  
Odile Filhol ◽  
Claude Cochet ◽  
Annette K. Larsen
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Topoisomerase Ii ◽  
Dna Topoisomerase Ii ◽  
Dna Topoisomerase ◽  
Topoisomerase Ii Α ◽  
Mitotic Phosphorylation ◽  
Kinase Ck2

scholarly journals Specific binding of protein kinase CK2 catalytic subunits to tubulin

FEBS Letters ◽  
1999 ◽  
Vol 462 (1-2) ◽  
pp. 51-56 ◽  
Author(s):  
Michael Faust ◽  
Norbert Schuster ◽  
Mathias Montenarh
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Specific Binding ◽  
Catalytic Subunits ◽  
Kinase Ck2

Protein kinase CK2 from two higher eukaryotes of economical importance, the mussel Mytilus galloprovincialis and the medfly Ceratitis capitata

2012 ◽  
Vol 7 (2) ◽  
pp. 185-191
Author(s):  
Sophia Kouyanou-Koutsoukou ◽  
Andrea Baier ◽  
Regina-Maria Kolaitis ◽  
Ryszard Szyszka
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Mytilus Galloprovincialis ◽  
Ceratitis Capitata ◽  
Marine Pollution ◽  
Cell Cycle Control ◽  
Control Of Gene Expression ◽  
Catalytic Subunits ◽  
Wide Range ◽  
Kinase Ck2

AbstractProtein kinase CK2 is a highly conserved Ser/Thr protein kinase involved in cell cycle control, transcription, signal transduction and cell proliferation. It is upregulated in several diseases and by oxidative stress. CK2 is generally composed of two catalytic subunits and two regulatory subunits and utilizes either ATP or GTP as a phosphate donor. CK2 was isolated from the sea mussel Mytilus galloprovincialis, a biomarker of marine pollution, and the Mediterranean fly Ceratitis capitata, an insect capable of wreaking extensive damage to a wide range of fruit crops with great economical importance. The catalytic CK2α and regulatory CK2β subunits of M. galloprovincialis and C. capitata show similar properties. The mussel and fly catalytic subunits and holoenzymes were capable of phosphorylating the recombinant ribosomal stalk P1 protein, implying functional conservation. They also demonstrate the characteristics of a typical CK2: use of ATP and GTP as phosphate donors, inhibition by known modulators of CK2 activity (like benzotriazole derivatives and heparin), and stimulation by polycations. Both organisms seem to be ideal models for the analysis of CK2 in the control of gene expression in response to cellular stress.

Phosphorylation and Pin1 binding to the LIC1 subunit selectively regulate mitotic dynein functions

2021 ◽  
Vol 220 (12) ◽  
Author(s):  
Amrita Kumari ◽  
Chandan Kumar ◽  
Rajaiah Pergu ◽  
Megha Kumar ◽  
Sagar P. Mahale ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Mitotic Progression ◽  
Prolyl Isomerase ◽  
Developmental Defects ◽  
Dynein Motor ◽  
Chromosome Congression ◽  
Golgi Fragmentation ◽  
Mitotic Phosphorylation ◽  
Early Developmental ◽  
Ctd Phosphorylation

The dynein motor performs multiple functions in mitosis by engaging with a wide cargo spectrum. One way to regulate dynein’s cargo-binding selectivity is through the C-terminal domain (CTD) of its light intermediate chain 1 subunit (LIC1), which binds directly with cargo adaptors. Here we show that mitotic phosphorylation of LIC1-CTD at its three cdk1 sites is required for proper mitotic progression, for dynein loading onto prometaphase kinetochores, and for spindle assembly checkpoint inactivation in human cells. Mitotic LIC1-CTD phosphorylation also engages the prolyl isomerase Pin1 predominantly to Hook2-dynein-Nde1-Lis1 complexes, but not to dynein-spindly-dynactin complexes. LIC1-CTD dephosphorylation abrogates dynein-Pin1 binding, promotes prophase centrosome–nuclear envelope detachment, and impairs metaphase chromosome congression and mitotic Golgi fragmentation, without affecting interphase membrane transport. Phosphomutation of a conserved LIC1-CTD SP site in zebrafish leads to early developmental defects. Our work reveals that LIC1-CTD phosphorylation differentially regulates distinct mitotic dynein pools and suggests the evolutionary conservation of this phosphoregulation.

Specific localization of the catalytic subunits of protein kinase CK2 at the centrosomes

2002 ◽  
Vol 59 (12) ◽  
pp. 2155-2164 ◽  
Author(s):  
M. Faust ◽  
J. Günther ◽  
E. Morgenstern ◽  
M. Montenarh ◽  
C. Götz
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Catalytic Subunits ◽  
Specific Localization ◽  
Kinase Ck2

scholarly journals Crystal structures of human CK2α2 in new crystal forms arising from a subtle difference in salt concentration

2018 ◽  
Vol 74 (5) ◽  
pp. 288-293 ◽  
Author(s):  
Masato Tsuyuguchi ◽  
Tetsuko Nakaniwa ◽  
Takayoshi Kinoshita
Keyword(s):  
Crystal Structure ◽  
Crystal Structures ◽  
Protein Kinase Ck2 ◽  
Selective Inhibitors ◽  
Subtle Difference ◽  
Catalytic Subunits ◽  
Crystal Forms ◽  
Male Contraceptive ◽  
Kinase Ck2 ◽  
Drug Discovery Target

The catalytic subunits of protein kinase CK2 are classified into two subtypes: CK2α1 and CK2α2. CK2α1 is an attractive drug-discovery target for various diseases such as cancers and nephritis. CK2α2 is defined as an off-target of CK2α1 and is a potential target in the development of male contraceptive drugs. High-resolution crystal structures of both isozymes are likely to provide crucial clues for the design of selective inhibitors of CK2α1 and/or CK2α2. To date, several crystal structures of CK2α1 have been solved at high resolutions of beyond 1.5 Å. However, crystal structures of CK2α2 have barely achieved a low resolution of around 3 Å because of the formation of needle-shaped crystals. In this study, new crystal forms were exploited and one provided a crystal structure of CK2α2 at 1.89 Å resolution. This result, together with the structure of CK2α1, will assist in the development of highly selective inhibitors for both isozymes.

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