Jing, H. | bioRxiv Science

bioRxiv2018

Impact of Premorbid Infection on Onset and Disease Activity of Rheumatoid Arthritis

ObjectiveInfections have been implicated in rheumatoid arthritis (RA) development. However, the impact of premorbid infection on initiation and perpetuation of RA has not been well elucidated. Thus, we sought to conduct a large scale on-site survey to study whether premorbid infection may trigger RA and influence status of the disease.\n\nMethodsPremorbid infectious events were collected in cohort of 902 RA patients from December 2015 to June 2016. Type of infections prior to RA onset and its possible effects on disease status were analyzed.\n\nResultThree hundred and thirty-four out of 902 patients (37.03%) experienced infections within one month preceding RA onset. The most frequent infections were respiratory (16.08%), intestinal (11.09%) and urinary tract (9.87%) infection, respectively. The infection was associated with increased disease activity. Early onset was found in patients with urinary infection. High disease activity risk was increased in patients who pre-exposure to urinary infection (OR=3.813, 95%CI=1.717-12.418) and upper respiratory infection (OR=2.475, 95%CI= 0.971-6.312).\n\nConclusionPre-exposure infections are associated with development of RA. Severe disease status of RA and persistent of active disease status are related to preceding infections.

epidemiology↗

bioRxiv2017

SIRT2 and lysine fatty acylation regulate the oncogenic activity of K-Ras4a

Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a. We further demonstrate that SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of K-Ras4a, enhances its interaction with A-Raf, and thus promotes cellular transformation. Our study identifies lysine fatty acylation as a previously unknown regulatory mechanism for the Ras family of GTPases that is distinct from cysteine fatty acylation. These findings highlight the biological significance of lysine fatty acylation and sirtuin-catalyzed protein lysine defatty-acylation.

biochemistry↗