Search results for "Cyclin-Dependent Kinase"
showing 10 items of 164 documents
Molecular evolution of the metazoan protein kinase C multigene family
1996
Protein kinases C (PKCs) comprise closely related Ser/Thr kinases, ubiquitously present in animal tissues ; they respond to second messengers, e.g., Ca2+ and/or diacylglycerol, to express their activities. Two PKCs have been sequenced from Geodia cydonium, a member of the lowest multicellular animals, the sponges (Porifera). One sponge G. cydonium PKC, GCPKC1, belongs to the ''novel'' (Ca2+-independent) PKC (nPKC) subfamily while the second one, GCPKC2, has the hall-marks of the ''conventional'' (Ca2+-dependent) PKC (cPKC) subfamily. The alignment of the Ser/Thr catalytic kinase domains, of the predicted aa sequences for these cDNAs with respective segments from previously reported sequence…
Alteration of DNA topoisomerase II activity during infection of H9 cells by human immunodeficiency virus type 1 in vitro: a target for potential ther…
1990
Infection of H9 cells with human immunodeficiency virus type 1 (HIV-1) was found to decrease the phosphorylation of DNA topoisomerase II during the initial phase of infection. Simultaneously, with a later overshoot of phosphorylation and the subsequent activation of DNA topoisomerase II, the production of HIV-1 started. Applying three new protein kinase C inhibitors from the class of O-alkylglycerophospholipids we demonstrated that inhibition of protein kinase C-mediated phosphorylation of DNA topoisomerase II resulted in an inhibition of HIV-1 production. Based on the differential effect of the two protein kinase C activators, phorbol ester and bryostatin, we conclude that phosphorylation …
Ciprofibrate stimulates protein kinase C-dependent phosphorylation of an 85 kDa protein in rat Fao hepatic derived cells
2000
The effect of ciprofibrate on early events of signal transduction was previously studied in Fao cells. Protein kinase C (PKC) assays performed on permeabilized cells showed a more than two-fold increase in PKC activity in cells treated for 24 h with 500 microM ciprofibrate. To show the subsequent effect of this increase on protein phosphorylation, the in vitro phosphorylation on particulate fractions obtained from Fao cells was studied. Among several modifications, the phosphorylation of protein(s) with an apparent molecular mass of 85 kDa was investigated. This modification appeared in the first 24 h of treatment with 500 microM ciprofibrate. It was shown to occur on Ser/Thr residue(s). It…
How a Second Mg2+ Ion Affects the Phosphoryl-Transfer Mechanism in a Protein Kinase: A Computational Study
2020
Mg2+ ions are essential for the proper functioning of protein kinases, and their roles in kinase activity have been studied for years. However, recent investigations have shed light on how these me...
How a Second Mg2+ Ion Affects the Phosphoryl Transfer Mechanism in a Protein Kinase: A Computational Study
2020
<div>In this contribution, the phosphoryl transfer reaction in CDK2 has been studied in detail considering the presence of an additional Mg2+ ion in the active site. For this purpose, QM/MM (quantum mechanics/molecular mechanics) free energy calculations with the adaptive string method were performed, which showed that indeed the system containing two Mg2+ ions exhibits a lower activation free energy, corroborating the experimental observations.</div>
Modulation of protein phosphorylation by natural products
2002
Studies carried out to determine the influence of phosphorylation and dephosphorylation of proteins in a variety of physiological events are of increasing interest. The activity of kinases and phosphatases and their respective inhibition by endogenous mediators and by pharmacological agents regulates a huge number of biochemical pathways involved in cellular proliferation, apoptosis, inflammation, hormonal activity, and gene transcription, amongother processes. This article focuses on the recently described natural products able to interfere negatively with the activity of serine/threonine and tyrosine kinases. These agents are classified, according to theirbiosynthetic origin and chemical …
Artemisinin–Second Career as Anticancer Drug?
2015
Artemisinin represents a showcase example not only for the activity of medicinal herbs deriving from traditional chinese medicine, but for phytotherapy in general. Its isolation from Sweet Wormwood (qinhao, Artemisia annua L.) represents the starting point for an unprecedent success story in the treatment of malaria worldwide. Beyond the therapeutic value against Plasmodium parasites, it turned out in recent years that the bioactivity of artemisinin is not restricted to malaria. We and others found that this sesquiterpenoid also exerts profound anticancer activity in vitro and in vivo. Artemisinin-type drugs exert multi-factorial cellular and molecular actions in cancer cells. Ferrous iron …
Cell Cycle: The Life Cycle of a Cell
2013
“Where a cell arises, there must be a previous cell”. This early statement of Rudolf Virchow already points to the process that is called cell cycle. It describes a series of events leading to cell division and duplication and can be sectioned into phases that are controlled by a collection of proteins interacting with each other, the cyclines and the cycline-dependent kinases. It is mandatory that DNA replication is conservative meaning that its structure and sequence remain unaltered while the DNA is duplicated before the cell actually divides. Checkpoints are responsible for the supervision, proteins such as p53 and RB being the key protagonists in cell cycle control. Upon DNA damage rec…
Increased dosage of Ink4/Arf protects against glucose intolerance and insulin resistance associated with aging
2013
Recent genome-wide association studies have linked type-2 diabetes mellitus to a genomic region in chromosome 9p21 near the Ink4/Arf locus, which encodes tumor suppressors that are up-regulated in a variety of mammalian organs during aging. However, it is unclear whether the susceptibility to type-2 diabetes is associated with altered expression of the Ink4/Arf locus. In the present study, we investigated the role of Ink4/Arf in age-dependent alterations of insulin and glucose homeostasis using Super-Ink4/Arf mice which bear an extra copy of the entire Ink4/Arf locus. We find that, in contrast to age-matched wild-type controls, Super-Ink4/Arf mice do not develop glucose intolerance with agi…
Genetic profile and immunohistochemical study of clear cell renal carcinoma: Pathological-anatomical correlation and prognosis.
2021
Abstract Introduction Renal cell carcinoma (RCC) accounts for 2–3% of all tumors being the most frequent solid lesion in the kidney. Objective To determine what genetic alterations and immunohistochemical (IHC) of clear cell renal carcinoma (ccRCC) are associated with prognosis and tumor aggressiveness. Patients and Methods Experimental analytical study with 57 patients who underwent radical and partial nephrectomy between 2005 and 2011, all with diagnosis of ccRCC and minimum post-operative follow-up of 36 months. The pathological study included IHC determination of biomarkers associated (CAIX, CAM 5.2, CD10, c-erbB-2, EGFR, HIF-1a, Ki67, MDM2, PAX-2 y 8, p53, survivin and VEGFR 1 and 2). …