Activities in progress

Human glandular kallikrein 2 (hK2) is a trypsin-like serine protease expressed predominantly in the prostate epithelium. Recently, hK2 has proven to be a useful marker that can be used in combination with prostate specific antigen for screening and diagnosis of prostate cancer. The cleavage by hK2 of certain substrates in the proteolytic cascade suggest that the kallikrein may be involved in prostate cancer development; however, there has been very little other progress toward its biochemical characterization or elucidation of its true physiological role.

8p system191 01-06-2013 45 2   Download

Mammalian G1 phase progression is regulated by G1 cyclin and cyclin-dependent kinases (cdks). Cdk4 or cdk6 is associated with D-type cyclins while cdk2 binds to cyclin E or cyclin A to become an independent and essential kinase [1,2]. Cdk3 is another putative G1 cdk, whose cyclin partners have not been identified [3]. In vitro, cdk3 is an active kinase in association with either cyclin E or cyclin A [4,5].

7p system191 01-06-2013 47 4   Download

Matrilysin (matrix metalloproteinase-7) plays important roles in tumor progression. It was previously found that matrilysin binds to the surface of colon cancer cells to promote their metastatic potential. In this study, we identified annexin II as a novel membrane-bound substrate of matrilysin. Treatment of human colon cancer cell lines with active matrilysin released a 35 kDa annexin II form, which lacked its N-terminal region, into the culture supernatant. The release of the 35 kDa annexin II by matrilysin was significantly enhanced in the presence of serotonin or heparin....

14p research12 29-04-2013 40 2   Download

The selective manipulation of the expression and replica-tion of mitochondrial DNA (mtDNA) within mammalian cells has proven difficult. In progressing towards this goal we synthesized a novel mitochondria-targeted DNA-alkylating reagent. The active alkylating moiety [(11aS)-8-hydroxy-7-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c] [1,4]benzodiazepin-5-one (DC-81)], irreversibly alkylates guanine bases in DNA (with a preference for AGA tri-plets), preventing its expression and replication.

10p fptmusic 16-04-2013 33 4   Download

Rio1 is the founding member of the RIO family of atypical serine kinases that are universally present in all organisms from archaea to mammals. Activity of Rio1 was shown to be absolutely essential inSaccharomyces cerevisiaefor the processing of 18S ribosomal RNA, as well as for proper cell cycle progression and chromosome maintenance. We determined high-resolution crystal structures ofArchaeoglobus fulgidusRio1 in the presence and absence of bound nucleotides.

16p fptmusic 11-04-2013 30 2   Download

The effects of high hydrostatic pressure (HHP) and urea on conformational transitions of humana-thrombin structure were studiedbyfluorescence spectroscopy andbymeasuring the catalytic activity of the enzyme. Treatment of thrombin with urea produced a progressive red shift in the center of mass of the intrinsic fluorescence emission spectrum, with a maximum displacement of 650 cm )1 . HHP (270 MPa) shifted the centre ofmass by only 370 cm )1 .HHP combined with a subdenaturing urea concentration (1.5M) displaced the centre of mass by
750 cm )1 ....

8p dell39 03-04-2013 27 3   Download

Nitric oxide (NO • ) has been proposed to be a physiological modulator of cell proliferation, able to promote in most cases cell cycle arrest. In this review I explore the molecular basis of this mechanism of action. The mod-ulatory action of NO • on the intracellular concentration of cGMP and the machinery directly involved in the control of cell cycle progression, inclu-ding the expression and activity of diverse cyclins and cyclin-dependent kinases,

16p inspiron33 26-03-2013 49 4   Download

Cyclins form complexes with cyclin-dependent kinases. By controlling activity of the enzymes, cyclins regulate progression through the cell cycle. A- and B-type cyclins were discovered due to their distinct appearance in S and G2 phases and their rapid proteolytic destruction during mitosis. Transition from G2 to mitosis is basically controlled by B-type cyclins.

15p inspiron33 26-03-2013 48 4   Download

The contributions of human DNA polymerases (pols)a, dande during S-phase progression were studied in order to elaborate how these enzymes co-ordinate their functions during nuclear DNA replication. Pol d was three to four times more intensely UV cross-linked to nascent DNA in late compared with early S phase, whereas the cross-linking of pols aande remained nearly constant throughout the S phase.

18p inspiron33 25-03-2013 66 4   Download

Exposure to quartz particles induces a pathological process named silicosis. Alveolar macrophages initiate the disease through their activation, which is the origin of the later dysfunctions. Ascorbic acid is known to selectively dissolve the quartz surface. During the reaction, ascorbic acid progressively disappears and hydroxyl radicals are generated from the quartz surface. These observations may be relevant to mammalian quartz toxicity, as sub-stantial amounts of ascorbic acid are present in the lung epithelium. ...

14p inspiron33 23-03-2013 41 4   Download

Hepatocyte growth factor activator (HGFA) is a serine protease and a potent activator of prohepatocyte growth factor⁄scatter factor (pro-HGF⁄SF), a multifunctional growth factor that is critically involved in tis-sue morphogenesis, regeneration, and tumor progression.

15p media19 06-03-2013 30 3   Download

The first enzyme of carnitine biosynthesis is the mitochondrial 6-N-tri-methyllysine dioxygenase, which converts 6-N-trimethyllysine to 3-hydroxy-6-N-trimethyllysine. Using progressive membrane solubilization with digitonin and protease protection experiments, we show that this enzyme is localized in the mitochondrial matrix.

7p media19 05-03-2013 19 2   Download

Breast cancer cells exhibit excessive proteolysis, which is responsible for extensive extracellular matrix degradation, invasion and metastasis. Besides other proteases, lysosomal cysteine protease cathepsin B has been impli-cated in these processes and the impairment of its intracellular activity was suggested to reduce harmful proteolysis and hence diminish progression of breast tumors.

12p media19 04-03-2013 50 2   Download

Ubiquitin specific protease 7 (USP7) belongs to the family of deubiquitinat-ing enzymes. Among other functions, USP7 is involved in the regulation of stress response pathways, epigenetic silencing and the progress of infections by DNA viruses.

15p media19 04-03-2013 40 3   Download

The purpose of this review is to discuss the effect of natural antioxidant compounds as modulators of the 20Sproteasome, a multi-enzymatic multi-catalytic complex present in the cytoplasm and nucleus of eukaryotic cells and involved in several cellular activities such as cell-cycle progression, pro-liferation and the degradation of oxidized and damaged proteins.

15p vinaphone15 28-02-2013 59 3   Download

Our recent studies have shown that, as indicated by vagal stimulation, an acetylcholinesterase inhibitor donepezil, an anti-Alzheimer’s disease drug, prevents progression of heart failure in rats with myocardial infarction, and activates a common cell survival signal shared by acetylcholine (ACh) in vitro.

15p vinaphone15 25-02-2013 33 3   Download

The role of thiamin diphosphate (ThDP) as a cofactor for enzymes has been known for many decades. This minireview covers the progress made in understanding the catalytic mechanism of ThDP-dependent enzymes through the use of ThDP analogues. Many such analogues have been syn-thesized and have provided information on the functional groups necessary for the binding and catalytic activity of the cofactor.

12p viettel02 22-02-2013 37 3   Download

All cells, from prokaryotes to vertebrates, synthesize enormous amounts of rRNA to produce 1–2 million ribosomes per cell cycle, which are required to maintain the protein synthesis capacity of the daughter cells. In recent years, considerable progress has been made in the elucidation of the basic principles of transcriptional regulation and the pathways that adapt cellular rRNA synthesis to metabolic activity, a process that is essential for under

14p viettel02 19-02-2013 41 1   Download

Heparanase is an endo-b-D-glucuronidase capable of cleaving heparan sul-fate side chains at a limited number of sites, yielding heparan sulfate frag-ments of still appreciable size. Importantly, heparanase activity correlates with the metastatic potential of tumor-derived cells, attributed to enhanced cell dissemination as a consequence of heparan sulfate cleavage and remod-eling of the extracellular matrix and basement membrane underlying epithe-lial and endothelial cells.

14p viettel02 19-02-2013 42 3   Download

Hepatocyte growth factor activator (HGFA) is a serine protease initially identified as a potent activator of hepatocyte growth factor⁄scatter factor. Hepatocyte growth factor⁄scatter factor is known to be critically involved in tissue morphogenesis, regeneration, and tumor progression, via its recep-tor, MET. In vivo, HGFA also activates macrophage-stimulating protein, which has roles in macrophage recruitment and inflammatory processes, cellular survival and wound healing through its receptor, RON....

8p mobifone23 21-01-2013 34 5   Download