Target intelligence / Profile preview

Host cell transcriptional machinery

Molecular classification
Enzyme, Transcription factor, Protein complex
01

Overview

The host cell transcriptional machinery is a complex multi-component system, primarily centered around RNA polymerase II (Pol II), responsible for the synthesis of messenger RNA (mRNA) from DNA templates (Source: Nature Reviews Molecular Cell Biology, 2017). This machinery includes a vast array of general transcription factors (GTFs), co-activators, and cyclin-dependent kinases like CDK9, which are essential for the initiation, elongation, and termination of transcription (Source: UniProt). In the context of viral infections, many viruses, such as HIV-1 and SARS-CoV-2, hijack this host apparatus to express their own genomes (Source: Cell Host & Microbe, 2020). In oncology, the machinery is often dysregulated, leading to the constitutive expression of growth-promoting genes like MYC (Source: Trends in Cancer, 2018). Therapeutic agents like Actinomycin D and Flavopiridol target this machinery by intercalating DNA or inhibiting regulatory kinases, respectively (Source: PubChem). However, because transcription is a fundamental life process, targeting this machinery often results in significant systemic toxicity and a narrow therapeutic window (Source: NIH/StatPearls).

Other names
Cellular transcription apparatusHost transcription systemRNA polymerase II complexTranscription machinery
02

Mechanism of action

Inhibition of RNA polymerase II activity, blockade of transcription initiation or elongation, and inhibition of cyclin-dependent kinases (CDKs) that regulate the transcriptional cycle.

03

Biological functions

Gene expressionRNA synthesisCell cycle regulationViral replication
04

Disease associations

InfectionCancerInflammation
05

Safety considerations

Systemic toxicityNarrow therapeutic indexHepatotoxicityMyelosuppressionOff-target effects on essential cellular genes
06

Interacting drugs

Actinomycin D

5 more in the full profile.

07

Biomarkers

RNA polymerase II phosphorylation statusGlobal mRNA expression levelsC-myc expression levels

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