Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Mediator is a multiprotein transcriptional coactivator that is expressed ubiquitously in eukaryotes from yeast to mammals and is required for induction of RNA polymerase II (pol II) transcription by DNA binding transcription factors. In the work described here, we exploit multidimensional protein identification technology (MudPIT) to carry out a proteomic analysis of the subunit composition of the mammalian Mediator complex. By comparing MudPIT data sets obtained from six independent Mediator preparations immunoaffinity purified through their Nut2 (MED10), Med25 (MED9), Intersex (MED29), LCMR1 (MED19), AK007855 (MED28), or CRSP70 (MED26) subunits, we identify a set of consensus mammalian Mediator subunits. In addition, we identify as Mediator-associated proteins the CDK8-like cyclin-dependent kinase CDK11 and the TRAP240-like KIAA1025 protein (MED13L), which is mutated in patients with the congenital heart defect transposition of the great arteries (TGA).
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PMID:A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. 1517 63

Mediator complex subunit 29 (MED29) is part of a large multiprotein coactivator complex that mediates regulatory signals from gene-specific activators to general transcription machinery in RNA polymerase II mediated transcription. We previously found that MED29 is amplified and overexpressed in pancreatic cancer and that MED29 silencing leads to decreased cell survival in PANC-1 pancreatic cancer cells with high MED29 expression. Here we further demonstrate decreased migration, invasion and colony formation in PANC-1 cells after MED29 silencing. Unexpectedly, lentiviral-based overexpression of MED29 led to decreased proliferation of NIH/3T3 cells as well as MIAPaCa-2 pancreatic cancer cells with low endogenous expression. More importantly, subcutaneous inoculation of the MED29-transduced pancreatic cancer cells into immuno-compromised mice resulted in dramatic tumor suppression. The mock-control mice developed large tumors, whereas the animals with MED29-xenografts showed both decreased tumor incidence and a major reduction in tumor size. Gene expression analysis in the MED29-transduced pancreatic cancer cells revealed differential expression of genes involved in control of cell cycle and cell division. The observed gene expression changes are expected to modulate the cell cycle in a way that leads to reduced cell growth, explaining the in vivo tumor suppressive phenotype. Taken together, these data implicate MED29 as an important regulator of key cellular functions in pancreatic cancer with both oncogenic and tumor suppressive characteristics. Such a dualistic role appears to be more common than previously thought and is likely to depend on the genetic background of the cancer cells and their surrounding environment.
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PMID:MED29, a component of the mediator complex, possesses both oncogenic and tumor suppressive characteristics in pancreatic cancer. 2122 29