A5068000268- Protein Kinase Regulation and GTPase Signaling
- Heat shock proteins research
- Cell death mechanisms and regulation
- PI3K/AKT/mTOR signaling in cancer
- Chronic Lymphocytic Leukemia Research
- Cancer-related Molecular Pathways
- Endoplasmic Reticulum Stress and Disease
- Cancer Mechanisms and Therapy
- Monoclonal and Polyclonal Antibodies Research
- Chronic Myeloid Leukemia Treatments
- Protein Tyrosine Phosphatases
- Enzyme Structure and Function
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Microtubule and mitosis dynamics
- Nitric Oxide and Endothelin Effects
- Quinazolinone synthesis and applications
- Research on Leishmaniasis Studies
- Multiple Myeloma Research and Treatments
- Pancreatic function and diabetes
- Autophagy in Disease and Therapy
- Glycosylation and Glycoproteins Research
- Computational Drug Discovery Methods
- Signaling Pathways in Disease
University of Padua
2015-2024
Neuroscience Institute
2008-2022
Veneto Institute of Molecular Medicine
2005-2014
National Research Council
2012
Magna Graecia University
2012
University of Modena and Reggio Emilia
2008
University of Dundee
2004
Medical Research Council
2004
Polish Academy of Sciences
2004
Beth Israel Deaconess Hospital
1997
The specificity of 4,5,6,7‐tetrabromo‐2‐azabenzimidazole (TBB), an ATP/GTP competitive inhibitor protein kinase casein kinase‐2 (CK2), has been examined against a panel 33 kinases, either Ser/Thr‐ or Tyr‐specific. In the presence 10 μM TBB (and 100 ATP) only CK2 was drastically inhibited (>85%) whereas three kinases (phosphorylase kinase, glycogen synthase 3β and cyclin‐dependent 2/cyclin A) underwent moderate inhibition, with IC 50 values one–two orders magnitude higher than (IC =0.9...
A systematic analysis reveals that out of 20 protein kinases examined, specific for either Ser/Thr or Tyr, the majority are extremely sensitive to staurosporine, with IC 50 values in low nanomolar range. few them however, notably CK1 and CK2, mitogen‐activated (MAP) kinase protein‐tyrosine CSK, relatively refractory staurosporine inhibition, exhibiting micromolar With all tested, namely PKA, CK1, MAP (ERK‐1), c‐Fgr, Lyn, CSK TPK‐IIB/p38 syk , inhibition was competitive respect ATP,...
CK2 (casein kinase 2) is a very pleiotropic serine/threonine protein whose abnormally high constitutive activity has often been correlated to pathological conditions with special reference neoplasia. The two most widely used cell permeable inhibitors, TBB (4,5,6,7-tetrabromo-1H-benzotriazole) and DMAT (2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole), are marketed as quite specific blockers. In the present study we show, by using panel of approx. 80 kinases, that its parent compound TBI...
Incubation of Jurkat cells with 4,5,6,7-tetrabromobenzotriazole (TBB), a specific inhibitor protein kinase CK2, induces dose-and time-dependent apoptosis as judged by several criteria. TBB-promoted is preceded inhibition Ser/Thr phosphorylation haematopoietic lineage cell-specific 1 (HS1) and accompanied caspase-dependent fragmentation the same protein. Both effects are also observable if promoted anti-Fas antibodies etoposide. Moreover, in vitro experiments show that HS1, once...
The relationship between nitric oxide (NO) and salicylic acid (SA) was investigated in Arabidopsis thaliana. Here it is shown that SA able to induce NO synthesis a dose-dependent manner Arabidopsis. production detected by confocal microscopic analysis spectrofluorometric assay plant roots cultured cells. To identify the metabolic pathways involved SA-induced synthesis, genetic pharmacological approaches were adopted. of nia1,nia2 mutant showed nitrate reductase activity not required for...
Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein whose abnormally high constitutive activity suspected to underlie its pathogenic potential in neoplasia infective diseases. Thus, CK2 inhibitors designed dissect the signaling pathways affected by this kinase, perspective, may give rise pharmacological tools. One of most successful TBB (4,5,6,7-tetrabromobenzotriazole). Here we show that inhibitory properties can be markedly improved generating adducts which N2...
Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a moderately potent and poorly selective inhibitor of protein kinase CK2, one the most pleiotropic serine/threonine kinases, implicated in neoplasia other global diseases. By virtual screening MMS (Molecular Modeling Section) database, we have now identified quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) as an CK2 that more than emodin. inhibition by competitive with respect to ATP, Ki value approx. 50 nM. Tested at 1 microM concentration...
Human genes coding for pLG72 and d-amino acid oxidase have recently been linked to the onset of schizophrenia. was proposed as an activator human FAD-containing flavoprotein (hDAAO). In brain this oxidizes d-serine, a potent N-methyl-d-aspartate receptor. We investigated mechanistic regulation hDAAO by pLG72. Immunohistochemical analyses revealed that are both expressed in astrocytes cortex, where they most likely interact, considering their partial overlapping subcellular distribution...
IQA {[5-oxo-5,6-dihydro-indolo(1,2-a)quinazolin-7-yl]acetic acid} is a novel ATP/GTP site-directed inhibitor of CK2 (‘casein kinase 2’), pleiotropic and constitutively active protein whose activity abnormally high in transformed cells. The Ki value (0.17 μM) lower than those other inhibitors reported so far. Tested at 10 μM concentration the presence 100 ATP, almost suppresses vitro, whereas it ineffective or weakly effective on panel 44 kinases phosphoinositide 3-kinase. In comparison,...
Abnormally high constitutive activity of protein kinase CK2, levels which are elevated in a variety tumours, is suspected to underlie its pathogenic potential. The most widely employed CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB), exhibits comparable efficacy toward another kinase, DYRK1 a. Here we describe the development new class inhibitors, conceptually derived from TBB, have lost their potency In particular, tetrabromocinnamic acid (TBCA) inhibits five times more efficiently than...
Abstract Purpose: Protein kinase CK2 promotes multiple myeloma cell growth by regulating critical signaling pathways. also modulates proper HSP90-dependent client protein folding and maturation phosphorylating its co-chaperone CDC37. Because the endoplasmic reticulum (ER) stress/unfolded response (UPR) is central in pathogenesis, we tested hypothesis that CK2/CDC37/HSP90 axis could be involved UPR cells. Experimental Design: We analyzed activity upon ER stress, effects of inactivation on...
Akt/PKB is a central activator of multiple signaling pathways coupled with large number stimuli. Although both localization and activity Akt in the nuclear compartment are well-documented, most substrates identified so far located cytoplasm, while have remained elusive. A proteomic-based search for was undertaken, exploiting 2D-electrophoresis/MS combination an anti-Akt phosphosubstrate antibody. This analysis indicated lamin A/C as putative substrate C2C12 cells. In vitro phosphorylation...