Andrea D'Osualdo

Publications (2)9.15 Total impact

• Article: NLRP1, a regulator of innate immunity associated with vitiligo.

  Andrea D'Osualdo, John C Reed
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  ABSTRACT: Some familial forms of the dermatological condition vitiligo have recently been linked to polymorphisms in the innate immunity gene, NLRP1. Here, we review what is currently known about the mechanisms that regulate activation of the NLRP1 protein and the downstream effects of NLRP1 on pathways impacting inflammation and apoptosis. How polymorphic variants of the NLRP1 gene contribute to the pathogenesis of vitiligo remains mysterious, requiring further investigation.
  Pigment Cell & Melanoma Research 11/2011; 25(1):5-8. · 5.06 Impact Factor
• Source

  Available from: PubMed Central

  Article: CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain.

  Andrea D'Osualdo, Christian X Weichenberger, Roland N Wagner, Adam Godzik, John Wooley, John C Reed
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  ABSTRACT: The "Function to Find Domain" (FIIND)-containing proteins CARD8 (Cardinal; Tucan) and NLRP1 (NALP1; NAC) are well known components of inflammasomes, multiprotein complexes responsible for activation of caspase-1, a regulator of inflammation and innate immunity. Although identified many years ago, the role of the FIIND is unknown. Here, we report that CARD8 and NLRP1 undergo autoproteolytic cleavage at a conserved SF/S motif within the FIIND. Using bioinformatics and computational modeling approaches, we detected striking structural similarity between the FIIND and the ZU5-UPA domain present in the autoproteolytic protein PIDD. This allowed us to generate a three-dimensional model and to gain insights in the molecular mechanism of the cleavage. Site-directed mutagenesis experiments revealed that the second serine of the SF/S motif is required for CARD8 and NLRP1 autoproteolysis. Furthermore, we discovered an important function for conserved glutamic acid and histidine residues, located in proximity of the cleavage site in regulating the autoprocessing efficiency. Altogether, these results identify a function for the FIIND and show that CARD8 and NLRP1 are ZU5-UPA domain-containing autoproteolytic proteins, thus suggesting a novel mechanism for regulating innate immune responses.
  PLoS ONE 01/2011; 6(11):e27396. · 4.09 Impact Factor