Linked Life Data

15882992

Source:http://linkedlifedata.com/resource/pubmed/id/15882992

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-5-10
pubmed:abstractText
CARD12 (Ipaf/Clan) is an important regulator of caspase-1 activation. It belongs to the family of the nucleotide-binding site and leucine-rich repeat (NBS-LRR) proteins. The NBS domain of the NBS-LRR proteins contains putative ATP/GTPase-specific P-loop and Mg2+-binding site motifs. However, the nucleotide-binding properties and the function of the NBS domain are unknown. We developed a nucleotide-binding assay and investigated nucleotide binding to CARD12. We find that the NBS domain of CARD12 contains a nucleotide-binding pocket with specificity for ATP/dATP. A point mutation in the P-loop (K175R) of the NBS domain abolishes ATP/dATP binding. We further demonstrate that the nucleotide-binding site is required for CARD12-mediated caspase-1 activation. CARD12 self-association and association with procaspase-1 in transfected cells were markedly decreased by the P-loop mutation K175R. Furthermore, the P-loop mutation greatly reduced caspase-1 activation-dependent proIL-1beta processing. Thus, CARD12 function is dependent on the nucleotide-binding site. Our data provide insights into the molecular mechanisms of CARD12-mediated caspase-1 activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
331
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1114-9
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Nucleotide binding to CARD12 and its role in CARD12-mediated caspase-1 activation.
pubmed:affiliation
Millennium Pharmaceuticals, Inc., 35 Landsdowne Street, Cambridge, MA 02139, USA. chafenlu@berkeley.edu
pubmed:publicationType
Journal Article