Cell Cycle Regulation of c-Jun N-Terminal Kinase Activity at the Centrosomes

2001 ◽  
Vol 289 (1) ◽  
pp. 173-180 ◽  
Author(s):  
Rebecca A. MacCorkle-Chosnek ◽  
Aaron VanHooser ◽  
David W. Goodrich ◽  
B.R. Brinkley ◽  
Tse-Hua Tan
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Kinase Activity ◽  
Cycle Regulation

scholarly journals Investigation of the cell cycle regulation of cdk3-associated kinase activity and the role of cdk3 in proliferation and transformation

Oncogene ◽  
1998 ◽  
Vol 17 (17) ◽  
pp. 2259-2269 ◽  
Author(s):  
Katja Braun ◽  
Gabriele Hölzl ◽  
Thomas Soucek ◽  
Christoph Geisen ◽  
Tarik Möröy ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Kinase Activity ◽  
Cycle Regulation

Kigamicin Induces Necrosis to Human Myeloma Cells by Disruption of Cell Cycle Regulation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5017-5017
Author(s):  
Miki Nakamura ◽  
Hiroyasu Esumi ◽  
Jie Lu ◽  
Hiroaki Mitsuya ◽  
Hiroyuki Hata
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Line ◽  
Cell Cycle Regulation ◽  
Kinase Activity ◽  
Myeloma Cell ◽  
Pi3 Kinase ◽  
Myeloma Cells ◽  
Pancreatic Cancer Cells ◽  
Cycle Regulation

Abstract Introduction Kigamicin (KM) is a compound isolated from Actinomycetes, which reportedly induces necrosis in pancreatic cancer cells under nutrient-starving condition but not under nutrient rich condition via PI3-kinase inhibition (Lu et al., Cancer Science 95, 547–52, 2004). Although the PI3-kinase activity is thought to be critical in the growth of myeloma cells, its actual role remains to be determined. In the present study, we evaluated KM’s anti-myeloma activity in both laboratory and primary myeloma cells and found that, contrary to the original finding in pancreatic cancer cells, KM induced necrosis in human myeloma cells both under nutrient-starving and nutrient-rich conditions. Results and discussion Myeloma cell lines (12PE and KHM-11) and primary myeloma cells purified with CD138-coated immune-magnetic beads were incubated with KM under nutrient-rich conditions. The CC50 value of KM for myeloma cells was approximately 100 nM after 24-hour exposure while pancreatic cancer cell line, PANC-1, did not show inhibition of viability even at 10 mM under nutrient-rich conditions, suggesting high sensitivity of myeloma cells to KM. When whole mononuclear cells obtained from a myeloma patient’s bone marrow were cultured with KM at a concentration of 500 nM in vitro, normal lymphocytes were spared while all myeloma cells underwent necrosis, suggesting that preferential cytotoxicity of KM in myeloma cells. Western blot analysis revealed that AKT phosphorylation decreased with KM treatment, suggesting that KM inhibits PI-3 kinase activity as previously reported. However, another pan-PI3 kinase inhibitor, LY294002, did not induce necrosis in myeloma cells, suggesting that PI3-kinase inhibition is not critically related to the cytotoxicity of KM in myeloma cells. A pan-caspase inhibitor, ZVAD-FMK, only partially inhibited cell death, suggesting that caspase is not involved in the cytotoxic function of KM, either. To further determine the mechanism of cytotoxicity in myeloma cells, a possible involvement of cyclin D1 and p21 was also examined. Western blot analysis revealed that KM completely reduced cyclin-D1 in myeloma cells. Moreover, KM induced translocation of p21 from cytoplasm to nucleus within 5 hours treatment, suggesting that KM disrupted cell cycle regulation. Finally, melphalan-resistant myeloma cell line, 11-EMS, showed significant cell death when exposed to KM even more efficiently than did melphalan-sensitive parental cell line, KHM-11. Since a number of anti-cancer reagents induce apoptosis in myeloma cells, KM induction of necrosis may represent a unique mechanism(s) and may overcome drug resistance of myeloma cells. Taking into a consideration a recent report by Lu et al. (Cancer Science 95, 547–52, 2004) showing that KM’s safe usage in a murine pancreatic cancer xenograft model, the present data suggest that KM could be a potential therapeutic agent for treatment of myeloma and warrant that further preclinial development of KM be continued.

scholarly journals Cell Cycle Regulation of the Saccharomyces cerevisiae Polo-Like Kinase Cdc5p

1998 ◽  
Vol 18 (12) ◽  
pp. 7360-7370 ◽  
Author(s):  
Liang Cheng ◽  
Linda Hunke ◽  
Christopher F. J. Hardy
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Kinase Activity ◽  
Anaphase Promoting Complex ◽  
Mitotic Kinases ◽  
Polo Kinase ◽  
Evolutionarily Conserved ◽  
M Phase ◽  
Cycle Regulation

ABSTRACT Progression through and completion of mitosis require the actions of the evolutionarily conserved Polo kinase. We have determined that the levels of Cdc5p, a Saccharomyces cerevisiae member of the Polo family of mitotic kinases, are cell cycle regulated. Cdc5p accumulates in the nuclei of G2/M-phase cells, and its levels decline dramatically as cells progress through anaphase and begin telophase. We report that Cdc5p levels are sensitive to mutations in key components of the anaphase-promoting complex (APC). We have determined that Cdc5p-associated kinase activity is restricted to G2/M and that this activity is posttranslationally regulated. These results further link the actions of the APC to the completion of mitosis and suggest possible roles for Cdc5p during progression through and completion of mitosis.

Meiosis-specific cell cycle regulation in maturing Xenopus oocytes

1994 ◽  
Vol 107 (11) ◽  
pp. 3005-3013 ◽  
Author(s):  
K. Ohsumi ◽  
W. Sawada ◽  
T. Kishimoto
Keyword(s):  
Cell Cycle ◽  
Meiotic Division ◽  
Cell Cycle Regulation ◽  
Xenopus Oocytes ◽  
Kinase Activity ◽  
S Phase ◽  
Cell Cycles ◽  
Minute Interval ◽  
Cycle Regulation ◽  
Meiosis I

Meiotic cell cycles differ from mitotic cell cycles in that the former lack S-phase in the interphase between meiosis I and meiosis II. To obtain clues for mechanisms involved in the cell cycle regulation unique to meiosis, we have examined changes in chromosomal morphology and H1 kinase activity during a meiotic period from metaphase I (MI) to metaphase II (MII) in Xenopus oocytes. Using populations of oocytes that underwent germinal vesicle breakdown (GVBD) within a 10 minute interval, we found that the kinase activity declined gradually during the 60 minute period after GVBD and then increased steadily during the following 80 minute interval, showing remarkable differences from the rapid drop and biphasic increase of the kinase activity in intermitotic periods (Solomon et al. (1990) Cell 63, 1013–1024; Dasso and Newport (1990) Cell 61, 811–823). We also found that the exit from MI lagged, by more than 30 minutes, behind the time of lowest H1 kinase activity, whereas the two events took place concomitantly at the end of meiosis II and mitosis. Consequently, the H1 kinase activity was already increasing during the first meiotic division. When H1 kinase activation at MII was delayed by a transient inhibition of protein synthesis after GVBD, oocytes were able to support formation of interphase nuclei and DNA replication between the first meiotic division and the MII arrest, indicating that the cell cycle entered S-phase between meiosis I and meiosis II. These results strongly suggest that the machinery required for entering S-phase has been established in maturing oocytes by the end of meiosis I.(ABSTRACT TRUNCATED AT 250 WORDS)

The Cyclin Interactor p26INCA1 Regulates the Hematopoietic Stem Cell Pool Via CDK Inhibition.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 637-637
Author(s):  
Nicole Baeumer ◽  
Sven Diederichs ◽  
Steffen Koschmieder ◽  
Boris V. Skryabin ◽  
Feng Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Cycle Regulation ◽  
Kinase Activity ◽  
Bone Marrow Cells ◽  
S Phase ◽  
Hematopoietic Stem ◽  
Cdk2 Activity ◽  
Cycle Regulation

Abstract Cell cycle progression is driven by the kinase activity of cyclin/CDK complexes. Dysregulation of the cell cycle leads to altered cell growth and contributes to tumorigenesis. Recently, we identified p26INCA1 as novel interaction partner of Cyclin A1/CDK2. Here, we characterize the phenotype of Inca1-null mice to uncover the cellular and molecular function of Inca1. Inca1-knockout mice were viable and fertile. FACS analyses revealed that aging mutant animals harbored an increased hematopoietic stem cell (HSC) pool. Bone marrow cells of young mice exhibited enhanced clonogenic replating efficiency in colony formation assays as compared to wildtype mice. Weekly administration of the myeloablative agent 5-fluorouracil (5-FU) led to a significantly shorter life span of Inca1−/ − mice compared to wildtype littermates. The increased 5-FU toxicity might thus be related to a higher number of cycling HSC in Inca1−/ − bone marrow. Analysis of the impact of Inca1 on cell cycle regulation demonstrated that the fraction of Inca1−/ − embryonic fibroblasts (MEFs) in S phase was significantly increased. Ectopic INCA1 expression reduced proliferation and colony formation of proliferating cells such as primary bone marrow cells, HeLa, HuTu80 and 32D cell lines. Serum starvation rapidly induced and mitogenic signals inhibited Inca1 expression providing a further link to cell cycle regulation. To identify the molecular mechanism of cell cycle regulation by Inca1, we investigated the influence of Inca1 on the direct inhibition of CDK2. In spleen lysates from Inca1-deficient mice, cellular CDK2 kinase activity towards Histone H1 was significantly induced compared to lysates of wildtype littermates. In in vitro kinase assays, recombinant INCA1 strongly inhibited CDK2 activity. In addition, we hypothesized that other cyclin kinase inhibitors (CKI) could partially compensate in vivo for the loss of Inca1 function. p21cip1/waf1 mRNA and protein expression were induced in Inca1−/ − MEFs compared to wildtype cells hinting at a partial compensation of the loss of Inca1 by induction of p21. Loss of Inca1 combined with p21 knockdown synergistically increased S-phase. These results indicate that Inca1 could be functionally related to p21 and that the rather mild phenotype observed in Inca1−/ − mice and the modest differences in Cdk activity observed in cell lysates lacking Inca1 could be due to compensatory induction of the CKI p21. In summary, loss of Inca1 increased cell proliferation, replating efficiency, S-phase progression, and Cdk2 activity whereas gain of Inca1 suppressed these cell functions. Inca1 expression was induced during cell cycle arrest. We conclude that Inca1 could be a novel cell cycle suppressor regulating the quiescence of HSCs through the inhibition of Cdk2.

Cell cycle regulation of histone H1 kinase activity associated with the adenoviral protein E1A

Science ◽  
1991 ◽  
Vol 253 (5025) ◽  
pp. 1271-1275 ◽  
Author(s):  
A Giordano ◽  
J. Lee ◽  
J. Scheppler ◽  
C Herrmann ◽  
E Harlow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Kinase Activity ◽  
Histone H1 ◽  
Cycle Regulation

scholarly journals Cla4p, a Saccharomyces cerevisiae Cdc42p-activated kinase involved in cytokinesis, is activated at mitosis.

1997 ◽  
Vol 17 (9) ◽  
pp. 5067-5076 ◽  
Author(s):  
B K Benton ◽  
A Tinkelenberg ◽  
I Gonzalez ◽  
F R Cross
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Specific Activity ◽  
Binding Domain ◽  
Kinase Assay ◽  
G1 Cyclins ◽  
Cycle Regulation

Yeasts have three functionally redundant G1 cyclins required for cell cycle progression through G1. Mutations in GIN4 and CLA4 were isolated in a screen for mutants that are inviable with deletions in the G1 cyclins CLN1 and CLN2. cln1 cln2 cla4 and cln1 cln2 gin4 cells arrest with a cytokinesis defect; this defect was efficiently rescued by CLN1 or CLN2 expression. GIN4 encodes a protein with strong homology to the Snflp serine/threonine kinase. Cla4p is homologous to mammalian p21-activated kinases (PAKs) (kinases activated by the rho-class GTPase Rac or Cdc42). We developed a kinase assay for Cla4p. Cla4p kinase was activated in vivo by the GTP-bound form of Cdc42p. The specific activity of Cla4p was cell cycle regulated, peaking near mitosis. Deletion of the Cla4p pleckstrin domain diminished kinase activity nearly threefold and eliminated in vivo activity. Deletion of the Cla4p Cdc42-binding domain increased kinase activity nearly threefold, but the mutant only weakly rescued cla4 function in vivo. This suggests that kinase activity alone is not sufficient for full function in vivo. Deletion of the Cdc42-binding domain also altered the cell cycle regulation of kinase activity. Instead of peaking at mitosis, the mutant kinase activity exhibited reduced cell cycle regulation and peaked at the G1/S border. Cla4p kinase activity was not reduced by mutational inactivation of gin4, suggesting that Gin4p may be downstream or parallel to Cla4p in the regulation of cytokinesis.

scholarly journals Cyclin I-like (CCNI2) is a cyclin-dependent kinase 5 (CDK5) activator and is involved in cell cycle regulation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Chengcheng Liu ◽  
Xiaoyan Zhai ◽  
Bin Zhao ◽  
Yanfei Wang ◽  
Zhigang Xu
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Mitotic Cell ◽  
Cyclin Dependent Kinase ◽  
Cellular Events ◽  
Cycle Regulation ◽  
Cyclin Dependent Kinase 5 ◽  
Cyclin I

Abstract In contrast to conventional cyclin-dependent kinases that are important for mitotic cell division, cyclin-dependent kinase 5 (CDK5) is predominantly activated in post-mitotic cells and is involved in various cellular events. The kinase activity of CDK5 is tightly regulated by specific activators including p35, p39, and cyclin I (CCNI). Here we show that cyclin I-like (CCNI2), a homolog of CCNI, interacts with CDK5 and activates the kinase activity of CDK5. Different from CCNI, which colocalizes with CDK5 in the nuclei in transfected cells, CCNI2 mainly retains CDK5 in the cytoplasm as well as on the cell membrane. Furthermore, although the expression level of CCNI2 mRNA and CCNI2 protein do not change significantly during cell cycle, depletion of CCNI2 with siRNA affects cell cycle progression as well as cell proliferation. In conclusion, our data strongly suggest that CCNI2 is a novel CDK5 activator and is involved in cell cycle regulation.

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