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 adenomatous polyposis coli (APC) tumour suppressor protein is a component of the Wnt signalling pathway in which it plays a major role in controlling nuclear accumulation of beta-catenin and hence in the modulation of beta-catenin-regulated gene transcription. APC also associates with microtubules at the ends of cytoplasmic extensions in epithelial cells, a distribution that can be reproduced in COS cells ectopically expressing APC. To examine the effect of APC on microtubule properties, we monitored directly the behaviour of APC and of APC-decorated microtubules by time-lapse imaging of cytoplasmic extensions in live COS cells expressing APC tagged with a green fluorescent protein. On the proximal part of microtubules, APC was visualised as particulate material moving unidirectionally towards the plus end of microtubules. The distal parts of microtubules were uniformly decorated by APC and were animated by a motile behaviour in the form of aperiodic bending. This behaviour is likely to be the consequence of compression forces acting on microtubules encountering obstacles while elongating. The majority of APC-decorated microtubules in transfected COS cells was sensitive to depolymerisation by nocodazole, but they contained detyrosinated and acetylated alpha-tubulin, suggesting a reduction in the rate of subunit exchange at their growing end. Taken together, these results demonstrate that microtubule domains uniformly decorated by APC display dynamic and motile properties that may be significant for the postulated role of APC in targeting microtubules to specialised membrane sites.
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PMID:Dynamic properties of APC-decorated microtubules in living cells. 1258 82

The yeast Sir2 (silent information regulator-2) protein functions as an NAD(+)-dependent histone deacetylase to silence gene expression from the mating-type locus, tolomeres and rDNA and also promotes longevity and genome stability in response to calorie restriction. Homologues of yeast Sir2 have been identified in the three domains of bacteria, archaea and eukaryotes; in mammalian cells, Sir2 proteins also deacetylate non-histone proteins such as the p53 tumour suppressor protein, alpha-tubulin and forkhead transcription factors to mediate diverse biological processes including metabolism, cell motility and cancer. We have determined the X-ray crystal structure of a Sir2 homologue from yeast Hst2 (yHst2), in various liganded forms, including the yHst2/acetyl-Lys-16 histone H4/NAD(+) ternary complex; we have also performed related biochemical studies to address the conserved mode of catalysis by these enzymes as well as the distinguishing features that allow different members of the family to target their respective cognate substrates. These studies have implications for the structure-based design of Sir2-specific small molecule compounds, which might modulate Sir2 function for therapeutic application.
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PMID:Structure and chemistry of the Sir2 family of NAD+-dependent histone/protein deactylases. 1550 20

The water extract of the lettuce Lactuca sativa, but not the ethyl acetate extract, inhibited the growth of HL-60 leukaemia cells and MCF-7 breast cancer cells. This correlated with the activation of checkpoint kinase 2 (Chk2), the induction of the tumour suppressor p21, and the severe downregulation of the proto-oncogene cyclin D1. The ethyl acetate extract, but not the water extract, induced HL-60 cell death, which correlated with the acetylation of alpha-tubulin. The acetylation of alpha-tubulin is indicative for microtubuli stabilisation such as induced by taxol. The calculated amount for human intake would require approximately 3 kg lettuce to reach the required concentration shown to inhibit 50% HL-60 proliferation.
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PMID:Anti-leukaemic effects of two extract types of Lactuca sativa correlate with the activation of Chk2, induction of p21, downregulation of cyclin D1 and acetylation of alpha-tubulin. 2020 3