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  • br Results br Discussion Previous studies have mapped ABCF

    2021-04-07


    Results
    Discussion Previous studies have mapped ABCF1 as a risk factor gene for rheumatoid arthritis and autoimmune pancreatitis (Ota et al., 2007, Richard et al., 1998). Additionally, recent genome-wide association studies have also associated ABCF1 with the risk of gout (Dong et al., 2017) and Crohn’s disease (Hindorff et al., 2009). The dysregulation of innate immune responses is thought to be a key factor for the prognosis of these immunological disorders, and current research is focusing on modulating cytokine secretion by macrophages. Given that ABCF1 negatively regulates MyD88-dependent TLR2 and TLR9 signaling, positively regulates TRIF-dependent TLR3 signaling, and is essential for the MyD88-to-TRIF transition during TLR4 signaling, it is likely that ABCF1 regulates innate immune responses, macrophage polarization, and cytokine production in these autoimmune disorders. Further work is required to understand the precise role of ABCF1 in the regulation of these diseases. For several decades, research has focused on discovering TLR4 inhibitors that control pathogenesis during sepsis (Wittebole et al., 2010). Here, we describe a keystone regulator that could control the understudied shift from the SIRS to ET phase of sepsis in patients, thereby modulating sepsis mortality. Thus, ABCF1 might be a potential target for pharmacological drug development to protect against sepsis. Further work is needed to exploit this target to modify patient outcomes in various diseases.
    STAR★Methods
    Acknowledgments
    Drought is a major environmental stress factor that significantly reduces crop growth and productivity. Through evolution, plants have developed various mechanisms in response to environmental stress, such as changes in their internal molecules, cellular processes and physiological processes (). Protein activity is modulated by adding small s6 kinase to the target protein, i.e., a process known as post- translational modification (PTM). PTM process is a quick, reversible physiological response needed by living organisms to respond to environmental changes. Several important protein modifiers exist and are used in PTM, including phosphate, methyl, acetyl, lipid, sugar and small peptide (). Ubiquitin is the most important small peptide associated with protein degradation, and the small ubiquitin-like modifier (SUMO) is one of many ubiquitin-like modifiers with a conformational structure and conjugation machinery similar to the ubiquitin system (, ). An essential post-translational regulatory process in all eukaryotes, SUMO conjugation (SUMOylation) involves three key enzymes: the SUMO activating enzyme (SAE/E1-type), SUMO conjugating enzyme (SCE1/E2-type) and SUMO ligase (E3-type) (). In , however, E4-type enzymes (PIAL1 and PIAL2) have been reported (). Activation of the SUMO carboxyl terminus, catalyzed by SAE/E1, leads to formation of a thioester and transfer of SUMO to a SUMO-conjugating enzyme (SCE1). Moreover, SCE/E2 links the SUMO carboxyl terminus to lysine ɛ-amino groups in the substrate, with or without the help of E3 ligases (, ). E4-type enzymes, PIAL1 and PIAL2, were previously reported to function as SUMO ligases, which are capable of SUMO chain formation but require the SUMO-modified SUMO conjugating enzyme SCE1 for optimal activity (). SUMOylation plays a role in different cellular processes and has been demonstrated a range of effects depending on its target (, ). Some SUMO modifications regulate transcription factor activities, which can correspond to gene expression for plant development, and responses to hormones and environmental cues (, , , ). In plants, SUMOylation is essential for development and stress responses (). , the role of SUMO conjugation in the stress response in has been described for various stresses, including drought (, , ), low temperature () and pathogens (). The role of SUMOylation in plants was previously reviewed by . In rice (), the transcripts of SUMOylation-related genes are identified under cold, salt and abscisic acid (ABA) stresses. Furthermore, SUMOylation-related genes show differential accumulation in various tissues during development, suggesting important roles in both rice development and stress responses ().