Inflammasome-mediated glucocorticoid resistance: The receptor rheostat. (2nd January 2016)

• Record Type: Journal Article
• Authors: Paugh, Steven W.; Bonten, Erik J.; Evans, William E.
• Is Part Of: Molecular & cellular oncology. Volume 3:Number 1(2016)
• Publication Date: 2016-01-02
• Subjects: CASP1 -- glucocorticoids -- inflammasome -- NALP3 -- NR3C1; Tumors -- Periodicals; Neoplasms; Periodicals; 616.99
• DOI: 10.1080/23723556.2015.1065947
• Languages: English
• ISSNs: 2372-3556

Abstract

ABSTRACT: In primary acute lymphoblastic leukemia cells exhibiting de novo resistance to glucocorticoids, we recently discovered decreased promoter methylation of caspase 1 ( CASP1 ) and NLR family, pyrin domain containing 3 ( NLRP3 ), which resulted in increased transcription, constitutive NALP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome activation, and caspase 1-mediated cleavage of the glucocorticoid receptor. This revealed a novel mechanism of glucocorticoid resistance that was recapitulated in model systems.