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Literature summary for 3.6.5.2 extracted from

  • Hsiao, B.Y.; Chang, T.K.; Wu, I.T.; Chen, M.Y.
    Rad GTPase inhibits the NFkappaB pathway through interacting with RelA/p65 to impede its DNA binding and target gene transactivation (2014), Cell. Signal., 26, 1437-1444.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
gene rad, recombinant expression of GST-tagged Rad in Escherichia coli Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
Homo sapiens 5737
-
nucleus the nuclear localization of Rad is important for its suppressive effect on NFkappaB Homo sapiens 5634
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
GTP + H2O Homo sapiens
-
GDP + phosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
additional information the enzyme expression is frequently lost in lung adenocarcinoma cells Homo sapiens
-
NCI-H1299 cell
-
Homo sapiens
-
NCI-H838 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
Homo sapiens GDP + phosphate
-
?

Synonyms

Synonyms Comment Organism
Rad
-
Homo sapiens
Ras-related small GTPase
-
Homo sapiens

General Information

General Information Comment Organism
malfunction overexpression of Rad in cells lowers both the basal and TNFalpha-stimulated transcriptional activity of NFkappaB. Compared with control cells, Rad-overexpressing cells display more cytoplasmic distribution of the NFkappaB subunit RelA/p65,while Rad knockdown cells have higher levels of nuclear RelA/p65. Depleting Rad does not affect the kinetics of TNFalpha-induced IkappaB degradation. Rad depletion alters the expression of an array of NFkappaB target genes, including upregulating MMP9, depletion of Rad enhances MMP9 expression and cell invasion. Knockdown of Rad expression in cells increases both basal and TNFalpha-stimulated MMP9 activities and cell invasion Homo sapiens
physiological function Rad is a Ras-related small GTPase shown to inhibit cancer cell migration, and its expression is frequently lost in lung cancer cells. Rad can negatively regulate the NFkappaB pathway. Rad-mediated regulation of NFkappaB is through an IkappaB-independent mechanism. Expression of a nucleus-localized mutant Rad is sufficient to inhibit the NFkappaB transcriptional activity, whereas expressing the scaffolding protein 14-3-3gamma to retain Rad in the cytoplasm alleviates the suppressive effect of Rad on NFkappaB. The Rad-p65 interaction primarily occurs in the nucleus. Rad may directly impede the interaction between RelA/p65 and DNA. Role of nuclear Rad in inhibiting the NFkappaB pathway function Homo sapiens