Lan K. Nguyen

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Ubiquitination, the covalent attachment of ubiquitin to target proteins, has emerged as a ubiquitous post-translational modification (PTM) whose function extends far beyond its original role as a tag for protein degradation identified three decades ago. Although sharing parallel properties with phosphorylation, ubiquitination distinguishes itself in(More)
In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches,(More)
BACKGROUND Feedback regulation plays crucial roles in the robust control and maintenance of many cellular systems. Negative feedbacks are found to underline both stable and unstable, often oscillatory, behaviours. We explore the dynamical characteristics of systems with single as well as coupled negative feedback loops using a combined approach of(More)
Feedback controls are central to cellular regulation. Negative-feedback mechanisms are well known to underline oscillatory dynamics. However, the presence of multiple negative-feedback mechanisms is common in oscillatory cellular systems, raising intriguing questions of how they cooperate to regulate oscillations. In this work, we studied the dynamical(More)
Protein degradation via ubiquitination is a major proteolytic mechanism in cells. Once a protein is destined for degradation, it is tagged by multiple ubiquitin (Ub) molecules. The synthesized polyubiquitin chains can be recognized by the 26S proteosome where proteins are degraded. These chains form through multiple ubiquitination cycles that are similar to(More)
Ubiquitin modification of cellular proteins commonly targets them for proteosomal degradation, but can also convey non-proteolytic functions. Over the past years, advances in experimental approaches have helped uncover the extensive involvement of ubiquitination in protein regulation. However, our understanding of the dynamics of the ubiquitination-related(More)
Oxygen is a crucial molecule for cellular function. When oxygen demand exceeds supply, the oxygen sensing pathway centred on the hypoxia inducible factor (HIF) is switched on and promotes adaptation to hypoxia by up-regulating genes involved in angiogenesis, erythropoiesis and glycolysis. The regulation of HIF is tightly modulated through intricate(More)
Living organisms often exist in uncertain environments where changes are the norm. Cellular systems therefore require resilient regulatory mechanisms for timely and stable adaptation. Among various regulation motifs, multiple feedback control emerges as a common theme. The tryptophan operon system in Escherichia coli regulates the production ofintracellular(More)
The detailed, atomistic-level understanding of molecular signaling along the tumor-suppressive Hippo signaling pathway that controls tissue homeostasis by balancing cell proliferation and death through apoptosis is a promising avenue for the discovery of novel anticancer drug targets. The activation of kinases such as Mammalian STE20-Like Protein Kinases 1(More)
Cyclooxygenase 2 (COX2), a key regulatory enzyme of the prostaglandin/eicosanoid pathway, is an important target for anti-inflammatory therapy. It is highly induced by pro-inflammatory cytokines in a Nuclear factor kappa B (NFκB)-dependent manner. However, the mechanisms determining the amplitude and dynamics of this important pro-inflammatory event are(More)