Protein ubiquitination is an important means of post-translational modification which plays an essential role in the regulation of various aspects of leukocyte development and function. The specificity of ubiquitin tagging to a protein substrate is determined by E3 ubiquitin ligases via defined E3-substrate interactions. In this review, we will focus on two E3 ligases, VHL and Itch, to discuss the latest progress in understanding their roles in the differentiation and function of CD4 T helper cell subsets, the stability of regulatory T cells, effector function of CD8 T cells, as well as the development and maturation of innate lymphoid cells. The biological implications of these E3 ubiquitin ligases will be highlighted in the context of normal and dysregulated immune responses including the control of homeostasis, inflammation, auto-immune responses and anti-tumor immunity. Further elucidation of the ubiquitin system in immune cells will help in the design of new therapeutic interventions for human immunological diseases and cancer.

BACKGROUND: Sedentary behaviors have recently become an important public health issue. We aimed to investigate the relationship between screen time and nutrient intake in children and adolescents. METHODS: The present study was conducted in 2013. Data were collected from children and adolescents aged between 6 and 15 years old in Shika town. Questionnaires were distributed to 1459 subjects, 1414 of whom participated in the study (96.9%). Sedentary behaviors were assessed based on participants' screen behaviors (television (TV) viewing, personal computer (PC) use, and mobile phone (MP) use). The main outcomes were the intake of nutrients from a validated food frequency questionnaire. Analysis of covariance (ANCOVA) was used to examine the significance of differences in nutrient intake estimates. Multivariate linear regression analyses, adjusting for age, BMI, and physical activity, were used to provide parameter estimates (β) and 95% CI for the relationship between screen time and nutrient intake. RESULTS: In boys, longer TV viewing times correlated or tended to correlate with a lower intake of protein, potassium, calcium, iron, vitamin K, vitamin B-2, and total dietary fiber. In girls, longer TV viewing times correlated with a lower intake of protein, sodium, calcium, vitamin D, and vitamin B-2. Longer TV viewing times correlated with a higher intake of n-6 fatty acids in girls. PC use was related or tended to be related to a lower intake of potassium, iron, vitamin K, and folic acid in boys, but not in girls. A relationship was observed between MP use and a lower intake of vitamin K in boys, and MP use and a higher intake of vitamin D in girls. CONCLUSIONS The present results revealed that longer TV viewing times are associated with less protein, minerals, vitamins, and total dietary fiber intake in children and adolescents. It was also revealed that boys with PC use have less minerals and vitamins. These results support the need to design intervention programs that focus on decreasing TV viewing time in both sexes and PC use in boys while encouraging adherence to dietary guidelines among children and adolescents.
Adolescent ; Body Mass Index ; Child ; Cross-Sectional Studies ; Diet ; Energy Intake ; Exercise ; Female ; Humans ; Japan ; Male ; Screen Time ; Sedentary Behavior ; Sex Factors ; Socioeconomic Factors