Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0847097 (
acidity
)
15,165
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
To investigate the role of acidic and phosphorylated amino acids in the function of the major transactivation domain (tau 1) of the glucocorticoid receptor, we have performed a mutagenesis study. Aspartic and glutamic acid residues were neutralized in clusters of 2 to 4 amino acids throughout the tau 1 domain. The activity of the mutant proteins was determined using transactivation assays in yeast and mammalian cells. Some acidic residues in the core region of tau 1 appear to play a minor role in tau 1 activity, but, generally, individual acidic residues are not critical for activity. Mutagenesis of five serine residues that are phosphorylated in the mouse glucocorticoid receptor and which are conserved in the human receptor did not affect the transactivation activity of the tau 1 domain in yeast. As in mouse cells, these serine residues are the predominant sites of phosphorylation for ectopically expressed receptor in yeast, since the mutant protein lacking all five sites had a severely reduced phosphorylation level. Mutant proteins in which larger numbers of acidic residues are neutralized show a progressive decrease in activity indicating that
acidity
in general is important for tau 1 function. However, our results are not consistent with the "acid blob" theory of
transactivator
function that has been suggested for some other activator proteins. Other putative roles for the
acidity
of tau 1 are discussed.
...
PMID:Role of acidic and phosphorylated residues in gene activation by the glucocorticoid receptor. 761 59
The cell nucleus-targeted delivery of therapeutic agents plays a critical role in cancer therapy, since the biological target of many anticancer therapeutics is the cell nucleus. However, multiple physiological barriers limit the delivery efficiency of free drugs, resulting in unsatisfactory therapeutic effects. Herein, thioketal crosslinked polyphosphoester-based nanoparticles with a tumor
acidity
(pH
e
)-sensitive
transactivator
of transcription (TAT) peptide (DA-masked TAT-decorating reactive oxygen species (ROS)-sensitive Ce6/DOX-loaded hyperbranched nanoparticles (
D
TRCD)) are explored for cascade nucleus-targeted drug delivery. Following administration,
D
TRCD experiences prolonged circulation by masking the targeting effect of its TAT peptide and then achieves enhanced tumor cell uptake and improved translocation into the perinuclear region by reactivating the TAT targeting capability in tumor tissue. Subsequently, ROS generated by
D
TRCD under 660 nm laser not only disrupts the nuclear membrane to allow entry into the nuclei but also triggers intracellular release of the payload in the nuclei. As evidenced by in vivo experiments, such pH
e
/photo dual-sensitive polymeric nanocarriers offer remarkable therapeutic effects, efficiently suppressing tumor growth. This multistage cascade nucleus-targeted drug delivery concept provides new avenues to develop nucleus-targeted drug delivery systems.
...
PMID:Direct Nucleus-Targeted Drug Delivery Using Cascade pH
e
/Photo Dual-Sensitive Polymeric Nanocarrier for Cancer Therapy. 3131 47
