Biomedical subjects

P Muganda

Publications and source records attributed to P Muganda.

3 recordsLinked to original sources

PubMed1998

The human cytomegalovirus IE2 86 kDa protein elevates p53 levels and transactivates the p53 promoter in human fibroblasts.

Human cytomegalovirus (HCMV), a herpesvirus, has previously been reported to elevate cellular p53 levels within infected human fibroblasts. Since this elevation was reported to be due to the expression of HCMV immediate early (IE) gene products within the fibroblasts, and the HCMV immediate early region encodes several predominant proteins, the identity of the protein responsible for this elevation was investigated. We report that the HCMV IE2 86 kDa protein was clearly found to be the major immediate early protein responsible for elevating p53 levels within the fibroblasts. We also report that the HCMV IE2 86 kDa protein was found to transactivate the p53 promoter 5-6 fold, thus explaining the 5-6 fold rate of increased p53 protein synthesis we find in the HCMV infected fibroblasts. Since transactivation of the p53 promoter was observed in IE2 86 kDa transfected as well as in HCMV infected fibroblasts, transactivation of the p53 gene, therefore, is part of the mechanism HCMV uses to elevate p53 levels in infected fibroblasts. This is the first report to implicate the HCMV IE2 86 kDa protein in the elevation of p53 levels in fibroblasts, as well as in the transactivation of the p53 promoter in these cells.

Cells, Cultured↗

PubMed1994

Human cytomegalovirus elevates levels of the cellular protein p53 in infected fibroblasts.

Human cytomegalovirus (HCMV), like other DNA tumor viruses, induces morphological transformation of cells in vitro and stimulates host cell macromolecular synthesis in infected cells. Since other DNA tumor viruses, such as simian virus 40 and adenovirus, have previously been shown to interact with cellular protein p53, we investigated whether infection of cells by HCMV would modulate cellular p53 levels. Our results indicate that HCMV elevates cellular p53 levels on the order of 10- to 20-fold in infected fibroblasts. The induction of elevated p53 levels was dependent upon the presence of active virus and was prevented by neutralizing antibody. The induction of elevated p53 levels was determined not to be due to virus-receptor interactions or HCMV late events. The induction of elevated p53 levels commenced at immediate-early times of the HCMV multiplication cycle (6 h postinfection) and reached maximal levels by 24 h postinfection, before most of the HCMV DNA synthesis was initiated. HCMV immediate-early proteins were clearly shown to be responsible for elevating p53 levels in infected fibroblasts; expression of HCMV immediate-early region 1 and 2 proteins resulted in elevation of p53 levels in transfected human fibroblasts. This is the first report of increased p53 levels caused by HCMV in infected fibroblasts.

Antigens, Viral↗

PubMedDate not supplied

Cyclic nucleotide metabolism in solid tumor tissues.

The examination of the regulation of the system of 3'-5' cyclic nucleotide monophosphates has only begun in cancer tissues. In human cancers, these studies are notably non-existent. However, in animal cancers, especially the Morris hepatomas, enough data has been gathered that, while risky, certain trends seem to begin to appear. Cyclic AMP is constant or lowered, while cyclic GMP is elevated in the fast growing hepatomas. Regulation of adenylate cyclase by protein hormones is reduced, while regulation by epinephrine may be increased. Binding of glucagon is decreased in the fast growing hepatomas. Guanylate cyclase, while being predominantly cytoplasmic in the normal liver, is predominantly membrane bound in the tumors. The liver enzyme is also readily stimulated by several chemical carcinogens. The cyclic GMP phosphodiesterases are decreased in these tumors; while the cAMP phosphodiesterases are increased. Although the cyclic nucleotide dependent protein kinases (histone as substrate) are altered in the hepatomas, observations of unique cyclic nucleotide binding proteins or cAMP independent protein kinases in cancer tissues may be of even greater significance for the development of or the maintenance of the neoplastic state of cells.

3',5'-Cyclic-AMP Phosphodiesterases↗