Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biochemical function of p27Kip1 as an inhibitor of cyclin-dependent kinases is well-established, but the role of p27 as a tumor suppressor depends on specific cellular contexts. Previous studies using p27 knockout mice on mixed C57BL/6J x 129/Sv strain background did not find a tumor suppressor role of p27 in the liver. An important feature of mouse liver tumorigenesis is strain-dependent tumor susceptibility. Here, we determined the role of p27 in liver tumorigenesis in C57BL/6J mice, a liver tumor resistant strain, in response to a diethylnitrosamine (DEN) and phenolbarbital (PB) two-stage carcinogenesis protocol. At 6 mo of age, while livers of DEN-PB treated p27+/+ and p27-/- C57BL/6J mice appeared morphologically normal, p27-/- livers, but not p27+/+ livers, contained readily detectable glucose-6-phosphatase (G6Pase)-deficient foci. At the 9-mo time point, p27-/- mice developed significantly enhanced liver tumor phenotypes than p27+/+ mice as demonstrated by increased numbers and sizes of liver surface nodules, increased liver-to-body weight ratios, and increased numbers of G6Pase-deficient nodules and histologically diagnosed foci and adenomas in liver sections. Hepatic lesions in p27-/- livers contained more proliferating hepatocytes than lesions in p27+/+ livers, while the numbers of apoptotic cells appeared similar in lesions of both genotypes. Unexpectedly, tumors in p27-/- livers contained only slightly elevated Cdk2 kinase activity compared with normal livers. These results reveal a liver tumor suppressor role of p27 in this resistant mouse strain, and the need to further study the role of Cdk2 kinase in liver tumor promotion by p27 inactivation.
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PMID:Inactivation of p27Kip1 promotes chemical mouse liver tumorigenesis in the resistant strain C57BL/6J. 1762 Mar 7

The wood frog (Rana sylvatica) is one of only a few vertebrate species that can survive extensive freezing of its body fluids during the winter. The mechanisms of natural freeze tolerance include metabolic rate depression to conserve energy and the implementation of cryoprotective strategies, especially the synthesis of huge amounts of glucose as a cryoprotectant. Liver is the main source of glucose production/export (and other cryoprotective actions) and plays a central role in freezing survival of the whole animal. Freezing is a multi-component stress that includes anoxia/ischemia due to the cessation of blood flow and dehydration of cells caused by ice accumulation in extracellular spaces. To help endure these stresses, cells need to suppress and reprioritize ATP-expensive cell functions. One of these is cell growth and proliferation, and we hypothesized that cell cycle arrest would be key to freezing survival. The present study examines the responses by key cell cycle components to freezing, anoxia and dehydration stresses in wood frog liver. Immunoblotting was used to investigate protein expression of Cdc 2, Cdks (2, 4, 6), and cyclins (A, B1, D1, E) as well as the phosphorylation states of Cdks (Thr14/Tyr15), the phosphatases Cdc25a (Ser76) and Cdc25c (Ser216) and the CIP/KIP Cdk inhibitors p21 (Thr145) and p27 (Thr187). Responses to 24 h freezing, 24 h anoxia and 40% dehydration as well as recovery from these stresses were analyzed. The results showed very similar responses by cell cycle components to anoxia or dehydration and were consistent with cell cycle suppression under stress and reversal during recovery. Freezing showed elements of cell cycle suppression, including reduced protein levels of Cdks and cyclins A and B1, but also showed unique responses by cyclin D1, Cdc25 phosphatases and p21/p27. These may be linked with alternative actions by these proteins that contribute to cryoprotection; e.g., an alternative action of cyclin D1 as a transcription factor may contribute to the upregulation of glucose-6-phosphatase, a key enzyme needed for the export of glucose cryoprotectant.
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PMID:Cell cycle regulation in the freeze tolerant wood frog, Rana sylvatica. 2251 May 73