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: EC:3.6.3.44 (
P-glycoprotein
)
13,344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Overexpression of MDR1 in breast cancer remains a major cause for the failure of chemotherapy. In the present report, we find
UHRF1
plays an important role in inhibiting MDR1 promoter activity by directly binding to the MDR1 promoter. Knockdown of
UHRF1
activates MDR1 promoter activity and expression, attenuates the binding of
UHRF1
and HDAC1 to the MDR1 promoter.Overexpression of
UHRF1
in NCI/ADR-RES cells can induce deacetylation of histones H3 and H4 on the MDR1 promoter, which is facilitated by recruitment of HDAC1 to the MDR1 promoter. Loss of histone acetylation is accompanied by loss of binding of the key transcription factor, MyoD, CBP and p300, locking in marked suppression of MDR1, increasing sensitivity of MDR cancer cells to cytotoxic drugs that are transported by
P-glycoprotein
(P-gp). The inhibition of MDR1 expression by
UHRF1
may provide potential ways to overcome multidrug resistance (MDR) in breast cancer treatment.
...
PMID:UHRF1 inhibits MDR1 gene transcription and sensitizes breast cancer cells to anticancer drugs. 2003 78
