Biochemistry of cancer

P-glycoprotein (Pgp), a membrane pump often responsible for the multidrug resistance of cancer cells, undergoes conformational changes in the presence of substrates/modulators, or upon ATP depletion, reflected by its enhanced reactivity with the UIC2 monoclonal antibody. When the UIC2-shift was elicited by certain modulators (e.g. cyclosporin A or vinblastine, but not with verapamil or Tween 80), the subsequent binding of other monoclonal anti-Pgp Ig sharing epitopes with UIC2 (e.g. MM12.10) was abolished [Nagy, H., Goda, K., Arceci, R., Cianfriglia, M., ´ Mechetner, E. & Szabo Jr, G.

6p system191 01-06-2013 62 7   Download

Department of Biochemistry, Eotvos Lorand University, and 2Biotechnology Research Group of the Hungarian Academy of Sciences, ´ ´ ´ ´ Pazmany setany 1/C, Budapest, Hungary The molecular mechanism of the autolysis of rat a-chymotrypsin B was investigated. In addition to the two already known autolytic sites, Tyr146 and Asn147, a new site formed by Phe114 was identified. The former two sites and the latter one are located in the autolysis and the interdomain loops, respectivel

9p system191 01-06-2013 36 4   Download

Departamento de Fisiologıa de la Nutricion, Instituto Nacional de Ciencias Medicas y Nutricion ‘Salvador Zubiran’, Mexico; ´ ´ ´ ´ ´ Departamento de Patologıa Experimental, Instituto Nacional de Ciencias Medicas y Nutricion ‘Salvador Zubiran’,Mexico; 3Department of Biochemistry, Wake Forest University Medical Center, Winston-Salem, North Carolina, USA Branched chain amino-acid aminotransferase (BCAT) activity is present in fetal liver but the developmental pattern of mitochondrial BCAT (BCATm) expression in rat liver has not been studied.

8p system191 01-06-2013 47 6   Download

A splicing factor SF2/ASF is a natural substrate for the kinase activity of human topoisomerase I. This study demonstrates that SF2/ASF inhibits DNA cleavage by human topoisomerase I induced by the anti-cancer agent camptothecin. The inhibition is independent of the phosphorylation status of SF2/ASF. We show that the inhibition did not result from binding of SF2/ASF to DNA that would hinder interactions between topoisomerase I and DNA. Neither it was a consequence of a loss of sensitivity of the enzyme to camptothecin.

7p research12 01-06-2013 39 5   Download

Mucin glycoproteins on breast cancer cells carry shortened carbohydrate chains. These partially deglycosylatedmucin 1 (MUC-1) structures are recognized by the monoclonal antibody SM3, which is being tested for its diagnostic utility. We used NMR spectroscopy to analyze the binding mode and thebindingepitopeof peptideandglycopeptideantigens to the SM3 antibody. The pentapeptide PDTRP and the glycopentapeptide PDT(O-a-D-GalNAc)RP are known lig-ands of the monoclonal antibody.

12p research12 29-04-2013 40 3   Download

Matrix metalloproteinase (MMP)-3 inhibited human MDA-MB-231 breast cancer cell invasion through recon-stituted basement membranein vitro. Inhibition of invasion was dependent upon plasminogen and MMP-3 activation, was impaired by the peptide MMP-3 inhibitor Ac-Arg-Cys-Gly-Val-Pro-Asp-NH2 and was associated with: rapid MMP-3-mediated plasminogen degradation to microplas-minogen and angiostatin-like fragments;

8p research12 23-04-2013 35 3   Download

As one of the most important families of non-natural poly-mers with the propensity to form well-defined secondary structures, theb-peptides are attracting increasing attention. The compounds incorporatingb-amino acid residues have found various applications in medicinal chemistry and biochemistry.The conformational pool ofb-peptides com-prises several periodic folded conformations, which can be classified as helices, and nonpolar and polar strands.The latter two are prone to form pleated sheets.

10p tumor12 20-04-2013 30 4   Download

Much of the basic biochemistry of antiplasmin was described more than 20 years ago and yet it remains an enigmatic member of the serine protease inhibitor (serpin) family. It possesses all of the characteristics of other inhibitory serpins but in addition it has unique N- and C-terminal exten-sions which significantly modify its activities. The N-terminus serves as a substrate for Factor XIIIa leading to crosslinking and incorporation of antiplasmin into a clot as it is formed.

6p fptmusic 12-04-2013 29 2   Download

Human glutamate carboxypeptidase II (GCPII) is a co-catalytic metallopeptidase and its putative catalytic domain is homologous to the aminopeptidases fromVibrio proteolyticus and Streptomyces griseus.In humans, the enzyme is expressed predominantly in the nervous system and theprostate.Theprostate form, termedprostate-specific membraneantigen, is overexpressed inprostate cancer and is used as a diagnostic marker of the disease.II

9p dell39 03-04-2013 39 4   Download

Tumour cells are often sensitized by interferons to the effects of tumour necrosis factor-a-related apoptosis-inducing ligand (TRAIL). We have demonstrated previously that TRAIL has an inhibitory effect on protein synthesis [Jeffrey IW, Bushell M, Tilleray VJ, Morley S & Clemens MJ (2002) Cancer Res62, 2272–2280] and we have therefore examined the consequences of prior interferon-atreatment for the sensitivity of transla-tion to inhibition by TRAIL.

11p inspiron33 25-03-2013 34 3   Download

Hepoxilins are biologically relevant epoxy-hydroxy eicosanoids synthesized through the 12S-lipoxygenase (12S-LOX) pathway of the arachidonic acid (AA) metabolism. The pathway is bifurcated at the level of 12S-hydro-peroxy-eicosatetraenoic acid (12S-HpETE), which can either be reduced to 12S-hydro-eicosatetraenoic acid (12S-HETE) or converted to hepoxilins.

10p galaxyss3 19-03-2013 21 1   Download

Papillomaviruses are small DNA tumor viruses that infect mammalian hosts, with consequences from benign to cancerous lesions. The Early pro-tein 2 is the master regulator for the virus life cycle, participating in gene transcription, DNA replication, and viral episome migration.

11p galaxyss3 19-03-2013 33 3   Download

Cyclin dependent kinase 4 is a key regulator of the cell cycle and its activ-ity is frequently deregulated in cancer. The activity of cyclin dependent kinase 4 is controlled by multiple mechanisms, including phosphorylation of tyrosine 17.

11p galaxyss3 07-03-2013 30 4   Download

Matrix metalloproteinase-9 (MMP-9) displays a preference for a broad range of substrates including extracellular matrix proteins and cytokines. MMP-9 plays an important role in physiological processes, as well as in inflammatory diseases and numerous cancers.

13p media19 05-03-2013 34 1   Download

Epidermal growth factor receptor (EGFR)-mediated signal transduction is often hyperactivated in tumour cells and therefore considered a promising target for cancer therapy. A number of computational models have been developed which describe the pathway in great detail.

13p media19 04-03-2013 39 3   Download

A major contributing factor to the development of breast cancer is decreased functional expression of breast cancer susceptibility gene 1, BRCA1. Another key contributor to tumorigenesis is hypoxia. Here we show that hypoxia increased the nuclear localization of BRCA1 in MCF-7 and MDA-MB-468 human breast cancer cell lines without changing its steady-state expression level.

10p media19 04-03-2013 49 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

X-Linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis protein family that is overexpressed in human can-cers. There is great interest in the development of XIAP inhibitors, which are predicted to promote apoptosis in cancer cells and thus have therapeutic potential.

11p vinaphone15 28-02-2013 29 2   Download

The hypothalamic decapeptide gonadotropin-releasing hormone (GnRH) is well known for its role in the control of pituitary gonadotropin secretion, but the hormone and receptor are also expressed in extrapituitary tissues and tumor cells, including epithelial ovarian cancers.

16p vinaphone15 28-02-2013 31 3   Download

Magnetic resonance spectroscopy studies are often carried out to provide metabolic information on tumour cell metabolism, aiming for increased knowledge for use in anti-cancer treatments. Accordingly, the presence of intense lipid signals in tumour cells has been the subject of many studies aiming to obtain further insight on the reaction of cancer cells to external agents that eventually cause cell death.

14p vinaphone15 27-02-2013 28 3   Download