Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Query: UMLS:C0338671 (
Steroids
)
9,479
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To study the role of post-transcriptional polyadenylation in the mechanism of estrogen action, we measured free nucleoplasmic poly(A) polymerase activity in intact uterine nuclei of immature rabbits at timed intervals after a single intravenous dose of estradiol (20 microgram/kg body weight). Uterine nuclear poly(A) polymerase activity was altered in a biphasic manner by estradiol treatment with maximal activities occurring at 0.5 h and 12 h of steroid administration, at which time periods they were about 2- and 3-fold higher than pretreatment levels, respectively. The later increase in the enzyme activity was totally abolished by a prior cycloheximide (0.5 mg/kg) administration, whereas the initial activation of poly(A) polymerase seemed to occur via mechanism(s) independent of protein synthesis. It thus appears that changes in uterine nuclear poly(A) polymerase closely resemble those previously reported for the activity of
RNA polymerase II
after estradiol treatment.
Steroids
1980 Dec
PMID:Early changes in nucleoplasmic poly(A) polymerase activity in immature rabbit uterus after estradiol administration. 625 77
Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with
RNA polymerase II
(Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing. Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer. In addition to its role in genomic signaling, MED12 has been implicated in non-genomic signaling by interacting with and activating TGF-beta receptor 2 in the cytoplasm. Recent structural studies have revealed extensive inter-domain interactions and complex architecture of the Mediator-Pol II complex, suggesting that Mediator is capable of reorganizing its conformation and composition to fit cellular needs. We propose that alterations in Mediator subunit expression that occur in various cancers could impact the organization and function of Mediator, resulting in changes in gene expression that promote malignancy. A better understanding of the role of Mediator in cancer could reveal new approaches to the diagnosis and treatment of Mediator-dependent endocrine cancers, especially in settings of therapy resistance.
Steroids
2018 05
PMID:The mediator complex in genomic and non-genomic signaling in cancer. 2915 17