The ubiquitin ligase LIN41/TRIM71 targets p53 to antagonize cell death and differentiation pathways during stem cell differentiation

Rapidity and specificity are characteristic features of proteolysis mediated by the ubiquitin-proteasome system. Therefore, the UPS is ideally suited for the remodeling of the embryonic stem cell proteome during the transition from pluripotent to differentiated states and its inverse, the generation of inducible pluripotent stem cells. The Trim-NHL family member LIN41 is among the first E3 ubiquitin ligases to be linked to stem cell pluripotency and reprogramming. Initially discovered in C. elegans as a downstream target of the let-7 miRNA, LIN41 is now recognized as a critical regulator of stem cell fates as well as the timing of neurogenesis. Despite being indispensable for embryonic development and neural tube closure in mice, the underlying mechanisms for LIN41 function in these processes are poorly understood. To better understand the specific contributions of the E3 ligase activity for the stem cell functions of LIN41, we characterized global changes in ubiquitin or ubiquitin-like modifications using Lin41-inducible mouse embryonic stem cells. The tumor suppressor protein p53 was among the five most strongly affected proteins in cells undergoing neural differentiation in response to LIN41 induction. We show that LIN41 interacts with p53, controls its abundance by ubiquitination and antagonizes p53-dependent pro-apoptotic and pro-differentiation responses. In vivo, the lack of LIN41 is associated with upregulation of Grhl3 and widespread caspase-3 activation, two downstream effectors of p53 with essential roles in neural tube closure. As Lin41-deficient mice display neural tube closure defects, we conclude that LIN41 is critical for the regulation of p53 functions in cell fate specification and survival during early brain development

Effect of pretreatments and processing conditions on the chemical, physical, microbiological and sensory characteristics of garlic paste

The influence of storage temperature of garlic bulb and chemical additives (including ascorbic acid, citric acid and potassium sorbate) on the chemical, physical, microbiological and sensory characteristics of garlic paste was evaluated. Formation of undesirable greenish pigment was avoided by storing fresh garlic bulbs at 25 and 40C. Moreover, heating bulbs to 40C a few minutes before processing facilitated skin removal. Garlic paste was processed, packed and thermally treated at 85C for 5 min. The color of garlic paste was affected by chemical treatment, temperature and storage period. The rate of color difference (ΔE) increase was divided into two linear periods with different slopes. Garlic paste exhibited pseudoplasticity with yield stress and flow adequately described by the Herschel-Bulkley model (r2 > 0.990). Both consistency index and apparent viscosity decreased with increase in temperature.Fil: Constenla, Diana Teresita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Lozano, Jorge Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentin