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 c-myc promoter is regulated by scores of signals, transcription factors, and chromatin components. The logic integrating these multiple signals remains unexplored. Recent evidence suggests that activated MYC expression is regulated in several phases: 1) conventional transcription factors trigger transcription by the RNA polymerase II (pol II) paused within the proximal promoter region. Concurrently (and probably consequently), newly arrived chromatin-remodeling complexes mobilize a nucleosome masking the far upstream element (FUSE), 1.7-kb upstream of the P2 start site; 2) binding by FUSE-binding proteins (first FBP3, then FBP); and 3) FBP-interacting repressor (FIR) binds FUSE and returns transcription to basal or steady-state levels. The recruitment and release of the FBPs and FIR is governed by FUSE-DNA conformation, itself controlled by dynamic supercoils propagated behind pol II. The organization and operation of the c-myc promoter make it difficult to inactivate, but sensitive to disturbances (translocations, viral insertions, amplification, and mutation) that disrupt the fine-tuning seen at its normal chromosomal context.
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PMID:How the c-myc promoter works and why it sometimes does not. 1864 1

c-myc and p53 networks control proliferation, differentiation, and apoptosis and are responsive to, and cross-regulate a variety of stresses and metabolic and biosynthetic processes. At c-myc, the far upstream element binding protein (FBP) and FBP-interacting repressor (FIR) program transcription by looping to RNA polymerase II complexes engaged at the promoter. Another FBP partner, JTV1/AIMP2, a structural subunit of a multi-aminoacyl-tRNA synthetase (ARS) complex, has also been reported to stabilize p53 via an apparently independent mechanism. Here, we show that in response to oxidative stress, JTV1 dissociates from the ARS complex, translocates to the nucleus, associates with FBP and co-activates the transcription of a new FBP target, ubiquitin-specific peptidase 29 (USP29). A previously uncharacterized deubiquitinating enzyme, USP29 binds to, cleaves poly-ubiquitin chains from, and stabilizes p53. The accumulated p53 quickly induces apoptosis. Thus, FBP and JTV1 help to coordinate the molecular and cellular response to oxidative stress.
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PMID:JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress. 2128 45