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Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation

(2015) JOURNAL OF IMMUNOLOGY. 194(5). p.2064-2067
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Abstract
The NLRP3 inflammasome is a multimeric protein complex that is assembled in response to a wide array of pathogens and danger-associated molecular patterns. Despite the ability of NLRP3 to respond to diverse cues, the mechanisms controlling the assembly of this complex are contested. Recently published studies showed that HOIL-1, a member of the linear ubiquitin chain assembly complex, contributes to activation of the NLRP3 inflammasome. SHARPIN, along with HOIP and HOIL-1, constitute the linear ubiquitin chain assembly complex. In this study, we examined whether SHARPIN is required for the activation of the NLRP3 inflammasome. Using Sharpin cpdm macrophages (deficient in SHARPIN expression), we demonstrate that SHARPIN is required for optimal activation of the NLRP3 inflammasome by both canonical and noncanonical stimuli. Furthermore, Sharpin cpdm macrophages had dramatic defects on both the NF-kappa B and MAPK pathways, suggesting a role in transcriptional priming of the NLRP3 inflammasome. In conclusion, our study identified SHARPIN as a novel regulator of the NLRP3 inflammasome.
Keywords
HOST-DEFENSE, ASSEMBLY COMPLEX, AIM2 INFLAMMASOME, LINEAR UBIQUITINATION, DERMATITIS, CASPASE-11

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Citation

Please use this url to cite or link to this publication:

MLA
Gurung, Prajwal, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. “Cutting Edge: SHARPIN Is Required for Optimal NLRP3 Inflammasome Activation.” JOURNAL OF IMMUNOLOGY 194.5 (2015): 2064–2067. Print.
APA
Gurung, P., Lamkanfi, M., & Kanneganti, T.-D. (2015). Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation. JOURNAL OF IMMUNOLOGY, 194(5), 2064–2067.
Chicago author-date
Gurung, Prajwal, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2015. “Cutting Edge: SHARPIN Is Required for Optimal NLRP3 Inflammasome Activation.” Journal of Immunology 194 (5): 2064–2067.
Chicago author-date (all authors)
Gurung, Prajwal, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2015. “Cutting Edge: SHARPIN Is Required for Optimal NLRP3 Inflammasome Activation.” Journal of Immunology 194 (5): 2064–2067.
Vancouver
1.
Gurung P, Lamkanfi M, Kanneganti T-D. Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation. JOURNAL OF IMMUNOLOGY. 2015;194(5):2064–7.
IEEE
[1]
P. Gurung, M. Lamkanfi, and T.-D. Kanneganti, “Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation,” JOURNAL OF IMMUNOLOGY, vol. 194, no. 5, pp. 2064–2067, 2015.
@article{5928328,
  abstract     = {The NLRP3 inflammasome is a multimeric protein complex that is assembled in response to a wide array of pathogens and danger-associated molecular patterns. Despite the ability of NLRP3 to respond to diverse cues, the mechanisms controlling the assembly of this complex are contested. Recently published studies showed that HOIL-1, a member of the linear ubiquitin chain assembly complex, contributes to activation of the NLRP3 inflammasome. SHARPIN, along with HOIP and HOIL-1, constitute the linear ubiquitin chain assembly complex. In this study, we examined whether SHARPIN is required for the activation of the NLRP3 inflammasome. Using Sharpin cpdm macrophages (deficient in SHARPIN expression), we demonstrate that SHARPIN is required for optimal activation of the NLRP3 inflammasome by both canonical and noncanonical stimuli. Furthermore, Sharpin cpdm macrophages had dramatic defects on both the NF-kappa B and MAPK pathways, suggesting a role in transcriptional priming of the NLRP3 inflammasome. In conclusion, our study identified SHARPIN as a novel regulator of the NLRP3 inflammasome.},
  author       = {Gurung, Prajwal and Lamkanfi, Mohamed and Kanneganti, Thirumala-Devi},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keywords     = {HOST-DEFENSE,ASSEMBLY COMPLEX,AIM2 INFLAMMASOME,LINEAR UBIQUITINATION,DERMATITIS,CASPASE-11},
  language     = {eng},
  number       = {5},
  pages        = {2064--2067},
  title        = {Cutting edge: SHARPIN is required for optimal NLRP3 inflammasome activation},
  url          = {http://dx.doi.org/10.4049/jimmunol.1402951},
  volume       = {194},
  year         = {2015},
}

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