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Literature summary for 2.7.11.10 extracted from

  • Gupta, S.C.; Prasad, S.; Reuter, S.; Kannappan, R.; Yadav, V.R.; Ravindran, J.; Hema, P.S.; Chaturvedi, M.M.; Nair, M.; Aggarwal, B.B.
    Modification of cysteine 179 of IkappaBalpha kinase by nimbolide leads to down-regulation of NF-kappaB-regulated cell survival and proliferative proteins and sensitization of tumor cells to chemotherapeutic agents (2010), J. Biol. Chem., 285, 35406-35417.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.11.10

Cloned(Commentary)

Cloned (Comment) Organism
expression of wild-type FLAG-tagged IKK-beta or FLAG-tagged IKK-beta mutant C179A in A-293 cells Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
nimbolide nimbolide inhibits TNF-alpha-induced p65 nuclear translocation and phosphorylation. Nimbolide binds to and inhibits IKK activation. It suppresses NF-betaB activation by inhibition of IkappaBbeta kinase, wild-type not IKKbeta mutant C179A, leading to suppression of IkappaBalpha phosphorylation and degradation, nuclear translocation, DNA binding, and gene transcription Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
 Homo sapiens 5737
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + [IkappaB protein] Homo sapiens the IkappaBalpha subunit of NF-kappaB is phosphorylated at serine residues 32 and 36 ADP + [IkappaB phosphoprotein]
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
HL-60 cell
-
 Homo sapiens
-
JURKAT cell
-
 Homo sapiens
-
K-562 cell
-
 Homo sapiens
-
KBM-5 cell
-
 Homo sapiens
-
MM1-S cell
-
 Homo sapiens
-
myeloid leukemia cell
-
 Homo sapiens
-
myeloma cell
-
 Homo sapiens
-
RPMI-8226 cell
-
 Homo sapiens
-
T-cell lymphoma cell
-
 Homo sapiens
-
U-266 cell
-
 Homo sapiens
-
U-937 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + [IkappaB protein] the IkappaBalpha subunit of NF-kappaB is phosphorylated at serine residues 32 and 36 Homo sapiens ADP + [IkappaB phosphoprotein]
-
 ?
ATP + [IkappaB protein] phosphorylation at Ser32 and Ser36 catalyzed by IkappaBalpha kinase Homo sapiens ADP + [IkappaB phosphoprotein]
-
 ?

Synonyms

Synonyms Comment Organism
IkappaBalpha kinase
-
 Homo sapiens
IKK
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens

General Information

General Information Comment Organism
malfunction suppression of NF-betaB activation by nimbolide is caused by inhibition of IkappaB kinase, which leads to suppression of IkappaBalpha phosphorylation and degradation, nuclear translocation, DNA binding, and gene transcription. Nimbolide suppresses TNF-alpha-induced tumor cell invasion and NF-kappaB activation in a not-cell-specific manner Homo sapiens
metabolism in resting cells, NF-kappaB is kept in an inactive state in the cytoplasm as a heterotrimer consisting of p50, p65, and IkappaB proteins, including IkappaBalpha, IkappaBbeta, and IkappaBepsilon. In response to activation signals, the IkappaBalpha subunit is phosphorylated at serine residues 32 and 36 and ubiquitinated at lysine residues 21 and 22, which target them for proteasome-mediated degradation Homo sapiens