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:6.5.1.2 (
DNA ligase
)
2,749
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
O
6
-Methylguanine-DNA methyltransferase (MGMT) is a
DNA repair enzyme
that removes the alkyl groups from the O
6
position of guanine and is then degraded via ubiquitin-mediated degradation. Previous studies indicated that 1,3-bis(2-chloroethyl)-1-nitrosourea (
BCNU
) facilitates the ubiquitination and degradation of MGMT in several types of cancer cells. However, the underlying mechanism of MGMT ubiquitination remains unclear. In this study, we demonstrated for the first time that ubiquitin-conjugating enzyme E2 B (UBE2B) is a novel regulator of MGMT ubiquitination mediated by
BCNU
in nasopharyngeal carcinoma (NPC) cells. The E3 ubiquitin ligase RAD18, a partner of UBE2B, is also involved in
BCNU
-mediated MGMT ubiquitination. Overexpression/knockdown of UBE2B enhanced/reduced
BCNU
-mediated MGMT ubiquitination. Surprisingly, UBE2B knockdown significantly increased
BCNU
cytotoxicity in NPC cells. Therefore, loss of UBE2B seems to disrupt ubiquitin-mediated degradation of alkylated MGMT. We found that UBE2B knockdown reduced MGMT activity, suggesting that loss of UBE2B leads to the accumulation of deactivated MGMT and suppresses MGMT protein turnover in
BCNU
-treated cells. These findings indicate that UBE2B modulates sensitivity to
BCNU
in NPC cells by regulating MGMT ubiquitination.
...
PMID:Ubiquitin-conjugating enzyme E2 B regulates the ubiquitination of O
6
-methylguanine-DNA methyltransferase and BCNU sensitivity in human nasopharyngeal carcinoma cells. 3044 27
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