Temporal regulation of cdc2 mitotic kinase activity and cyclin degradation in cell-free extracts of Xenopus eggs

1989 ◽  
Vol 1989 (Supplement 12) ◽  
pp. 99-116 ◽  
Author(s):  
M.-A. FELIX ◽  
J. PINES ◽  
T. HUNT ◽  
E. KARSENTI
Keyword(s):  
Kinase Activity ◽  
Temporal Regulation ◽  
Mitotic Kinase

Cdc28-Clb mitotic kinase negatively regulates bud site assembly in the budding yeast

2001 ◽  
Vol 114 (1) ◽  
pp. 207-218 ◽  
Author(s):  
C.G. Padmashree ◽  
U. Surana
Keyword(s):  
Kinase Activity ◽  
Budding Yeast ◽  
Critical Role ◽  
The Other ◽  
Yeast Saccharomyces Cerevisiae ◽  
Bud Formation ◽  
Temporal Regulation ◽  
Mitotic Kinase ◽  
Cortical Localization ◽  
Bud Site

In the budding yeast Saccharomyces cerevisiae, a prospective mother normally commences the formation of a daughter (the bud) only in the G(1) phase of the cell division cycle. This suggests a strict temporal regulation of the processes that initiate the formation of a new bud. Using cortical localization of bud site components Spa2 and Bni1 as an indicator of bud site assembly, we show that cells assemble a bud site following inactivation of the Cdc28-Clb mitotic kinase but prior to START. Interestingly, an untimely inactivation of the mitotic kinase is sufficient to drive cells to assemble a new bud site inappropriately in G(2) or M phases. The induction of Cdc28/Clb kinase activity in G(1), on the other hand, dramatically reduces a cell's ability to construct an incipient bud site. Our findings strongly suggest that the Cdc28-Clb kinase plays a critical role in the mechanism that restricts the timing of bud formation to the G(1) phase of the cell cycle.

scholarly journals BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Ning Jiang ◽  
Yihao Liao ◽  
Miaomiao Wang ◽  
Youzhi Wang ◽  
Keke Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Target Genes ◽  
Kinase Activity ◽  
Mitotic Kinase ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation ◽  
The Impact ◽  
Pharmacologic Inhibition

Abstract Background The incidence of bladder urothelial carcinoma (UC), a common malignancy of the urinary tract, is approximately three times higher in men than in women. High expression of the mitotic kinase BUB1 is associated with the occurrence and development of several cancers, although the relationship between BUB1 and bladder tumorigenesis remains unclear. Methods Using a microarray approach, we found increased BUB1 expression in human BCa. The association between BUB1 and STAT3 phosphorylation was determined through molecular and cell biological methods. We evaluated the impact of pharmacologic inhibition of BUB1 kinase activity on proliferation and BCa progression in vitro and in vivo. Results In this study, we found that BUB1 expression was increased in human bladder cancer (BCa). We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727. In addition, the findings that pharmacologic inhibition of BUB1 kinase activity significantly suppressed BCa cell proliferation and the progression of bladder cancer in vitro and in vivo were further verified. Finally, we found that the BUB1/STAT3 complex promoted the transcription of STAT3 target genes and that depletion of BUB1 and mutation of the BUB1 kinase domain abrogated this transcriptional activity, further highlighting the critical role of kinase activity in the activation of STAT3 target genes. A pharmacological inhibitor of BUB1 (2OH-BNPP1) was able to significantly inhibit the growth of BCa cell xenografts. Conclusion This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.

scholarly journals Cell cycle regulation of p34cdc2 kinase activity in Physarum polycephalum

1990 ◽  
Vol 96 (4) ◽  
pp. 683-689
Author(s):  
B. Ducommun ◽  
Y. Tollon ◽  
M. Gares ◽  
D. Beach ◽  
M. Wright
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Physarum Polycephalum ◽  
Kinase Activity ◽  
Histone H1 ◽  
Early Event ◽  
Binding Property ◽  
Kinase Activation ◽  
Regulatory Pathways ◽  
Mitotic Kinase

The regulation of the mitotic histone H1 kinase activity has been analyzed during the naturally synchronous cell cycle of Physarum polycephalum plasmodia. The universal binding property of the p13suc1 Schizosaccharomyces pombe gene product was used to precipitate and assay the cdc2 histone H1 kinase activity. The kinase activity peaks at the beginning of metaphase and its decline, which requires protein synthesis, appears to be an early event during the metaphase process. Microtubular poisons, temperature shifts and DNA synthesis inhibitors were used to perturb cell cycle regulatory pathways and characterize their effects on cdc2 kinase activation. Our results suggest that the full activation of the mitotic kinase requires at least two successive triggering signals involving microtubular components and DNA synthesis.

scholarly journals Cdc7 kinase stimulates Aurora B kinase in M-phase

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sayuri Ito ◽  
Hidemasa Goto ◽  
Kinue Kuniyasu ◽  
Mayumi Shindo ◽  
Masayuki Yamada ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Kinase Activity ◽  
Phosphorylation Site ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Mitotic Kinase ◽  
M Phase ◽  
Phase Progression ◽  
Autophosphorylation Site

AbstractThe conserved serine-threonine kinase, Cdc7, plays a crucial role in initiation of DNA replication by facilitating the assembly of an initiation complex. Cdc7 is expressed at a high level and exhibits significant kinase activity not only during S-phase but also during G2/M-phases. A conserved mitotic kinase, Aurora B, is activated during M-phase by association with INCENP, forming the chromosome passenger complex with Borealin and Survivin. We show that Cdc7 phosphorylates and stimulates Aurora B kinase activity in vitro. We identified threonine-236 as a critical phosphorylation site on Aurora B that could be a target of Cdc7 or could be an autophosphorylation site stimulated by Cdc7-mediated phosphorylation elsewhere. We found that threonines at both 232 (that has been identified as an autophosphorylation site) and 236 are essential for the kinase activity of Aurora B. Cdc7 down regulation or inhibition reduced Aurora B activity in vivo and led to retarded M-phase progression. SAC imposed by paclitaxel was dramatically reversed by Cdc7 inhibition, similar to the effect of Aurora B inhibition under the similar situation. Our data show that Cdc7 contributes to M-phase progression and to spindle assembly checkpoint most likely through Aurora B activation.

scholarly journals The Human Cytomegalovirus Virion Possesses an Activated Casein Kinase II That Allows for the Rapid Phosphorylation of the Inhibitor of NF-κB, IκBα

2007 ◽  
Vol 81 (10) ◽  
pp. 5305-5314 ◽  
Author(s):  
Maciej T. Nogalski ◽  
Jagat P. Podduturi ◽  
Ian B. DeMeritt ◽  
Liesl E. Milford ◽  
Andrew D. Yurochko
Keyword(s):  
Human Cytomegalovirus ◽  
Molecular Mechanisms ◽  
Kinase Activity ◽  
Human Fibroblasts ◽  
Casein Kinase Ii ◽  
Casein Kinase ◽  
Temporal Regulation ◽  
Protein Kinase Ckii

ABSTRACT We documented that the NF-κB signaling pathway was rapidly induced following human cytomegalovirus (HCMV) infection of human fibroblasts and that this induced NF-κB activity promoted efficient transactivation of the major immediate-early promoter (MIEP). Previously, we showed that the major HCMV envelope glycoproteins, gB and gH, initiated this NF-κB signaling event. However, we also hypothesized that there were additional mechanisms utilized by the virus to rapidly upregulate NF-κB. In this light, we specifically hypothesized that the HCMV virion contained IκBα kinase activity, allowing for direct phosphorylation of IκBα following virion entry into infected cells. In vitro kinase assays performed on purified HCMV virion extract identified bona fide IκBα kinase activity in the virion. The enzyme responsible for this kinase activity was identified as casein kinase II (CKII), a cellular serine-threonine protein kinase. CKII activity was necessary for efficient transactivation of the MIEP and IE gene expression. CKII is generally considered to be a constitutively active kinase. We suggest that this molecular characteristic of CKII represents the biologic rationale for the viral capture and utilization of this kinase early after infection. The packaging of CKII into the HCMV virion identifies that diverse molecular mechanisms are utilized by HCMV for rapid NF-κB activation. We propose that HCMV possesses multiple pathways to increase NF-κB activity to ensure that the correct temporal regulation of NF-κB occurs following infection and that sufficient threshold levels of NF-κB are reached in the diverse array of cells, including monocytes and endothelial cells, infected in vivo.

scholarly journals Mitotic timing is differentially controlled by A- and B-type cyclins and by CDC6 associated with a bona fide CDK inhibitor Xic1 in Xenopus laevis cell-free extract

2021 ◽  
Vol 65 (7-8-9) ◽  
pp. 487-496
Author(s):  
Mohammed El Dika ◽  
Lisa Wechselberger ◽  
Bilal Djeghout ◽  
Djamel Eddine Benouareth ◽  
Mohammed El Dika ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Kinase Activity ◽  
Cyclin A ◽  
Histone H1 ◽  
Cyclin B ◽  
Mitotic Kinase ◽  
M Phase ◽  
Bona Fide ◽  
Full Activation ◽  
Dependent Mechanism

The timing of the M-phase is precisely controlled by a CDC6-dependent mechanism inhibiting the mitotic histone H1 kinase. Here, we describe the differential regulation of the dynamics of this mitotic kinase activity by exogenous cyclin A or cyclin B in the Xenopus laevis cycling extracts. We show that the experimental increase in cyclin A modifies only the level of histone H1 kinase activity, while the cyclin B increase modifies two parameters: histone H1 kinase activity and the timing of its full activation, which is accelerated. On the other hand, the cyclin A depletion significantly delays full activation of histone H1 kinase. However, when CDC6 is added to such an extract, it inhibits cyclin B-associated histone H1 kinase, but does not modify the mitotic timing in the absence of cyclin A. Further, we show via p9 co-precipitation with Cyclin-Dependent Kinases (CDKs), that both CDC6 and the bona fide CDK1 inhibitor Xic1 associate with the mitotic CDKs. Finally, we show that the Xic1 temporarily separates from the mitotic CDKs complexes during the peak of histone H1 kinase activity. These data show the differential coordination of the M-phase progression by cyclin A- and cyclin B-dependent CDKs, confirm the critical role of the CDC6-dependent histone H1 kinase inhibition in this process, and show that CDC6 acts differentially through the cyclin B- and cyclin A-associated CDKs. This CDC6- and cyclins-dependent mechanism likely depends on the precisely regulated association of Xic1 with the mitotic CDKs complexes. We postulate that: i. the dissociation of Xic1 from the CDKs complexes allows the maximal activation of CDK1 during the M-phase, ii. the switch between cyclin A- and cyclin B-CDK inhibition upon M-phase initiation may be responsible for the diauxic growth of mitotic histone H1 kinase activity.

scholarly journals H3K79me3T80ph is a Novel Histone Dual Modification and a Mitotic Indicator in Melanoma

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Danielle R. Martinez ◽  
Hunter W. Richards ◽  
Qiushi Lin ◽  
Carlos A. Torres-Cabala ◽  
Victor G. Prieto ◽  
...  
Keyword(s):  
Tissue Microarray ◽  
Kinase Activity ◽  
Histone H3 ◽  
Aurora Kinase ◽  
Metastatic Potential ◽  
Methyltransferase Activity ◽  
Temporal Regulation ◽  
The Core ◽  
Clinical Behaviour

The current study characterizes the mitosis-associated histone dual modification on the core of histone H3: trimethylation of histone H3 lysine 79 and simultaneous phosphorylation of H3 threonine 80 (H3K79me3T80ph). Through the use of protein and microscopy-based techniques, we find that H3K79me3T80ph shares a similar spatial and temporal regulation as H3S10ph but additionally requires methyltransferase activity. In addition, we find that Aurora kinase activity is necessary for the catalysis of H3K79me3T80phin vivo. Finally, our analysis of H3K79me3T80ph using a tissue microarray indicates that H3K79me3T80ph marks a subset of primary cutaneous melanomas with metastatic potential indicating that H3K79me3T80ph may identify a subset of invasive melanomas with a more aggressive clinical behaviour.

Sign in / Sign up

Export Citation Format

Share Document