Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human hepatitis B virus (HBV) HBx protein is a small transcriptional activator that is essential for virus infection. HBx is thought to be involved in viral hepatocarcinogenesis because it promotes tumorigenesis in transgenic mice. HBx activates the RAS-RAF-mitogen-activated protein (MAP) kinase signaling cascade, through which it activates transcription factors AP-1 and NF-kappa B, and stimulates cell DNA synthesis. We show that HBx stimulates cell cycle progression, shortening the emergence of cells from quiescence (G0) and entry into S phase by at least 12 h, and accelerating transit through checkpoint controls at G0/G1 and G2/M. Compared with serum stimulation, HBx was found to strongly increase the rate and level of activation of the cyclin-dependent kinases CDK2 and CDC2, and their respective active association with cyclins E and A or cyclin B. HBx is also shown to override or greatly reduce serum dependence for cell cycle activation. Both HBx and serum were found to require activation of RAS to stimulate cell cycling, but only HBx could shorten checkpoint intervals. HBx therefore stimulates cell proliferation by activating RAS and a second unknown effector, which may be related to its reported ability to induce prolonged activation of JUN or to interact with cellular p53 protein. These data suggest a molecular mechanism by which HBx likely contributes to viral carcinogenesis. By deregulating checkpoint controls, HBx could participate in the selection of cells that are genetically unstable, some of which would accumulate unrepaired transforming mutations.
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PMID:Hepatitis B virus HBx protein deregulates cell cycle checkpoint controls. 747 68

Sequence variations within the genome of human papillomavirus (HPV) type 16 have been reported in different ethnic populations, with some evidence suggesting that non-European variants may confer higher oncogenic potential. HPV16 European (EUR) and Asian (As) variants were identified previously as two major variants in cervical cancer from Anyang, China. The evolutionary analysis of these variants revealed that several important sequence variations in the E6 and E2 genes were under positive selection pressure. The aim of this study was to evaluate the effects of these variations on E6 and E2 functions regarding p53 degradation and transcription regulation of the long control region (LCR). By Western blot analysis, a similar ability to degrade p53 was observed among EUR E6, As E6, EUR E6-L83V and As E6-E113D. A rare variation, EUR E6-R10G, was found to shorten the half-life of p53 more efficiently than the other variations. Unlike EUR E2 acting as a transcriptional activator or a repressor at different concentrations, As E2 showed a dose-dependent repression of LCR activity, about twofold stronger than EUR E2 in the luciferase reporter assays. Furthermore, the site-directed mutagenesis revealed that E232K, which is a linked variation in the hinge region of As E2, was responsible for its enhanced repression ability. Collectively, these data indicate the altered functions of HPV16 E6 and E2 by certain variations, which may influence the potential of viral carcinogenesis.
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PMID:Functional effects of sequence variations in the E6 and E2 genes of human papillomavirus 16 European and Asian variants. 2415 Jul 86