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)

Marek's disease (MD) is a lymphoproliferative disorder induced by a herpesvirus in chickens, its natural host. After an early cytolytic infection, the virus induces lymphomas in T-cells. These cells are latently infected with the virus, but very few viral transcripts or proteins are detectable. Although there are indications that some of these virus-encoded transcripts may be involved in tumourigenesis, the exact nature of the virus-cell interaction contributing towards the transformed phenotype is not completely understood. Among the transcripts the meq protein with basic leucine zipper (bZIP) characteristic of the fos/jun family of transcriptional activators is thought to play a major role in MDV-induced oncogenesis. Similarly the MDV-en-coded immediate early transcripts, ICP4, also seems to play an important role in latency and transformation. Apart from the virally-encoded factors, various host cell factors may be involved in the induction of tumours. Although not much work has been done in elucidating these factors, the possible role of tumour suppressor genes like p53, proto-oncogenes like Bcl-2 capable of blocking apoptosis, and telomerases in the induction of lymphomas are discussed. Some of the recent findings concerning the molecular mechanisms of interactions between MD virus and retroviruses are also presented.
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PMID:Molecular pathogenesis of Marek's disease-recent developments. 1864 17

In the last decade, numerous microRNAs (miRNAs) have been identified in diverse virus families, particularly in herpesviruses. Gallid alphaherpesvirus 2 (GaHV2) is a representative oncogenic alphaherpesvirus that induces rapid-onset T-cell lymphomas in its natural hosts, namely Marek's disease (MD). In the GaHV2 genome there are 26 mature miRNAs derived from 14 precursors assembled into three clusters, namely the Meq-cluster, Mid-cluster and LAT-cluster. Several GaHV2 miRNAs, especially those in the Meq-cluster (e.g. miR-M4-5p), have been demonstrated to be critical in MD pathogenesis and/or tumorigenesis. Interestingly the downstream Mid-cluster is regulated and transcribed by the same promoter as the Meq-cluster in the latent phase of the infection, but the role of these Mid-clustered miRNAs in GaHV2 biology remains unclear. We have generated the deletion mutants of the Mid-cluster and of its associated individual miRNAs in GX0101 virus, a very virulent GaHV2 strain, and demonstrated that the Mid-clustered miRNAs are not essential for virus replication. Using GaHV2-infected chickens as an animal model, we found that, compared with parental GX0101 virus, the individual deletion of miR-M31 decreased the mortality and gross tumour incidence of infected chickens while the deletion individually of miR-M1 or miR-M11 unexpectedly increased viral pathogenicity or oncogenicity, similarly to the deletion of the entire Mid-cluster region. More importantly, our data further confirm that miR-M11-5p, the miR-M11-derived mature miRNA, targets the viral oncogene meq and suppresses its expression in GaHV2 infection. We report here that members of the Mid-clustered miRNAs, miR-M31-3p and miR-M11-5p, potentially act either as oncogene or tumour suppressor in MD lymphomagenesis.
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PMID:Putative roles as oncogene or tumour suppressor of the Mid-clustered microRNAs in Gallid alphaherpesvirus 2 (GaHV2) induced Marek's disease lymphomagenesis. 2851 May 13