NLRP2

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NLRP2

A gene located on chromosome 19q13.42 that encodes a NLRP2 (i.e., NALP2), a pyrin-like protein involved in activating caspase-1 (CASP1) by Toll-like receptors. NALP2 suppresses TNF- and CD40-induced NFKB1 activity at the IKK complex by inhibiting TNF-induced NFKBIA degradation. When associated with PYCARD, NALP2 activates CASP1, leading to the secretion of the pro-inflammatory cytokine IL1B.
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Structures of Nbs1 domains alone [161,168, 169] and bound to a CTP1 peptide [161] or Mre11 [167, 170] have illuminated our knowledge of the eukaryotic-specific components.
Limbo et al., "Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair," Cell, vol.
Clapperton et al, "A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage," Cell, vol.
Electron microscopy has revealed that ATM binds to DNA in monomeric form and upon exposure to ionizing radiation ATM phosphorylates many proteins, including Chk2, p53, NBS1, and BRCA1 (Cortez et al., 1999).
ATM-dependent phosphorylation of BRCA1, NBS1 and two additional players in the NBS1 branch of the pathway the SMC1, a chromosomal structural maintenance protein and FANCD2, a Fanconi anemia complementation group D2 protein, both are needed for an intact intra-S phase checkpoint (Shiloh et al., 2003; Andrea et al., 2003).
The majority of HR repair is mediated by Rad52 epistasis group that includes the Rad51, Rad52, Rad54, Rad55, Rad57, MRE11 and NBS1 function in the initial sensor of the broken DNA ends (Sonoda et al., 2001).
A functional link between SIRT1 deacetylase and NBS1 in DNA damage response.
Huang, "The phosphorylation status of PAS-B distinguishes HIF-1alpha from HIF-2alpha in NBS1 repression," The EMBO Journal, vol.
Initiation and maintenance of the SASP requires the DDR proteins ATM, NBS1, and CHK2, but not p53 and pRb.
In A549 cells, [H.sub.2][O.sub.2] activates DDR through the Mre11 (MRN) complex of proteins (Mre11, Rad50, and Nbs1), which are essential for activation of telangiectasia mutated protein kinase (ATM), checkpoint kinase 2 (Chk2), and H2AX ([gamma]H2AX).
Rzeszowska-Wolny, "The influence of XPD, APE1, XRCC1, and NBS1 polymorphic variants on DNA repair in cells exposed to X-rays," Mutation Research--Genetic Toxicology and Environmental Mutagenesis, vol.