Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to identify the molecular mechanism of action of the isoflavone, genistein. Genistein at 0.15 mM caused MCF-7 apoptotic cell death, which was accompanied by cell cycle delay in the G2/M phase. Twenty-four hours post-treatment, 47.3% of the MCF-7 cells accumulated at G2/M, compared with 19.9% in the untreated controls. At 0.15 mM, genistein caused an increase in the steady-state levels of the wild-type tumour suppressor p53, which was attributed to stabilising the tumour suppressor protein, since p53 mRNA levels did not increase. Prior to the upregulation of p53, which became evident within 6 h of genistein treatment, there was increased bcl-2 phosphorylation at 30 min post-treatment. Although early changes (30-120 min) in the phosphotyrosine peptide patterns were not detected, after 24h, genistein inhibited phosphorylation of several peptides. These results suggest that genistein's dual roles of protein tyrosine kinase inhibitor and topoisomerase II inhibitor are essential for the initiation of apoptosis.
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PMID:Genistein inactivates bcl-2, delays the G2/M phase of the cell cycle, and induces apoptosis of human breast adenocarcinoma MCF-7 cells. 1002 17

Src was the first oncogene to be discovered, and the first protein tyrosine kinase. The study of how Src transforms cells has been a rich field that has lead to insights into the control of the cell cycle, the organization of the cytoskeleton, and growth factor-independent growth. Yet we still do not fully understand exactly what Src does. In normal cells, Src has been implicated in the control of cell division, the production of autocrine growth factors, the cell's survival response, as well as in cell motility. My laboratory has focused on the involvement of Src and related kinases in the response of cells to mitogenic growth factors. We have shown that the activity of Src kinases is necessary for cells to enter the cell cycle when treated with mitogens such as platelet-derived growth factor. Src activity initiates a signal transduction cascade, involving the adaptor protein Shc, which culminates in the transcriptional activation of the transcription factor Myc. Furthermore, we have also shown that this requirement for Src is abrogated in cells lacking the tumour suppressor p53, suggesting that another of Src's functions in normal cells is to suppress the actions of p53.
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PMID:Role of Src in signal transduction pathways. The Jubilee Lecture. 1202 16

Cellular growth and development are regulated by reversible phosphorylation of tyrosine residues in target proteins. Protein tyrosine phosphatases (PTPs) catalyse removal, and protein tyrosine kinases (PTKs) the addition of phosphate. Data from various sources support a role for PTKs in transformation and it has long been hypothesized that some PTPs will function as tumour suppressor genes. Specific PTPs are down-regulated in some tumours, sometimes in association with ectopic expression of PTKs. Alternatively, other PTPs dephosphorylate and activate PTKs, and are themselves oncogenic. Much current interest surrounds the clinical introduction of specific PTK inhibitors, whereas targeting of PTPs remains largely unexplored. Phosphatases represent 4% of the drugable human genome and PTPs appear an important new target for cancer therapy. Here we briefly, describe PTP structure and function. Secondly, we review experimental and clinical data, which support a role for PTPs in neoplastic development. Next, we review current strategies for generation of agents targeting PTPs; these include re-expression of tumour suppressor genes (mediated via adenoviral vectors), and generation of small molecules designed to inhibit oncogenic activity. Finally, we address the role of PTPs in melanoma, an increasingly common tumour that may represent an appropriate target for therapeutic manipulation of PTP activity.
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PMID:Protein tyrosine phosphatases, new targets for cancer therapy. 1701 75