KAT5 acetylates cGAS to promote innate immune response to DNA virus.

The DNA sensor cGMP-AMP synthase (cGAS) senses cytosolic microbial or self DNA to initiate a MITA/STING-dependent innate immune response. cGAS is regulated by various posttranslational modifications at its C-terminal catalytic domain. Whether and how its N-terminal unstructured domain is regulated by posttranslational modifications remain unknown. We identified the acetyltransferase KAT5 as a positive regulator of cGAS-mediated innate immune signaling. Overexpression of KAT5 potentiated viral-DNA-triggered transcription of downstream antiviral genes, whereas a KAT5 deficiency had the opposite effects. Mice with inactivated Kat5 exhibited lower levels of serum cytokines in response to DNA virus infection, higher viral titers in the brains, and more susceptibility to DNA-virus-induced death. Mechanistically, KAT5 catalyzed acetylation of cGAS at multiple lysine residues in its N-terminal domain, which promoted its DNA-binding ability. Our findings suggest that KAT5-mediated cGAS acetylation at its N terminus is important for efficient innate immune response to DNA virus.

MARCH3 attenuates IL-1ß-triggered inflammation by mediating K48-linked polyubiquitination and degradation of IL-1RI.

The proinflammatory cytokine IL-1ß plays critical roles in inflammatory and autoimmune diseases. IL-1ß signaling is tightly regulated to avoid excessive inflammatory response. In this study, we identified the E3 ubiquitin ligase membrane-associated RING-CH-type finger 3 (MARCH3) as a critical negative regulator of IL-1ß-triggered signaling. Overexpression of MARCH3 inhibited IL-1ß-triggered activation of NF-κB as well as expression of inflammatory genes, whereas MARCH3 deficiency had the opposite effects. MARCH3-deficient mice produced higher levels of serum inflammatory cytokines and were more sensitive to inflammatory death upon IL-1ß injection or Listeria monocytogenes infection. Mechanistically, MARCH3 was associated with IL-1 receptor I (IL-1RI) and mediated its K48-linked polyubiquitination at K409 and lysosomal-dependent degradation. Furthermore, IL-1ß stimulation triggered dephosphorylation of MARCH3 by CDC25A and activation of its E3 ligase activity. Our findings suggest that MARCH3-mediated IL-1RI degradation is an important mechanism for attenuating IL-1ß-triggered inflammatory response.

[Spatial variability and management zone of soil major nutrients in tobacco fields in Qiannan mountainous region].

Spatial variability and management zone of soil major nutrients in tobacco fields in Qian-nan mountainous region were analyzed using geostatistics and fuzzy c-mean algorithm. Results indicated that the level of soil organic matter (OM) was moderate, and alkalytic nitrogen (AN), available phosphorus (AP) and available potassium (AK) were rich according to tobacco soil nutrient classification standards. Coefficients of variation (CV) of OM, AN, AP and AK were moderate. Contents of OM, AN, AP and AK fitted log-normal distributions. Correlation analysis showed moderate correlations between OM and AN, AP and AK. OM and AN were best described by Gaussian semivariogram models, while AP and AK were described by exponential models. The four nutrients displayed moderate spatial autocorrelation. There were significant differences among lag distances of four soil nutrients. OM, AN, AP and AK in the majority of studied regions varied at moderate to very rich levels, and deficiencies of OM, AN, AP and AK only accounted for 0.93%, 0.53%, 0.24% and 7.91% of the total studied region, respectively. Based on the results, the studied region was divided into two management zones (MZ), namely MZ1 and MZ2, accounting for 69. 8% and 30. 2% of the studied region respectively. The soil levels of OM, AN, AP and AK in MZ1 were significantly lower than those in MZ2 (P < 0.01).