19 papers · ranked by Valyu relevance
Nader Alerasool, Zhen-Yuan Lin, Anne-Claude Gingras, Mikko Taipale
Transcription is orchestrated by thousands of transcription factors and chromatin-associated proteins, but how these are causally connected to transcriptional activation or repression is poorly understood. Here, we conduct an unbiased proteome-scale screen to systematically uncover human proteins that activate…
Urszula Luchowska-Stańska, David Morgan, Stephen J. Yarwood, Graeme Barker
'Graeme Barker'] The cellular signalling enzymes, EPAC1 and EPAC2, have emerged as key intracellular sensors of the secondary messenger cyclic 3′,5′-adenosine monophosphate (cyclic adenosine monophosphate) alongside protein kinase A. Interest has been galvanised in recent years thanks to the emergence of these species…
Abderahmane Derouiche, Lei Shi, Aida Kalantari, Ivan Mijakovic
Bacterial protein-tyrosine kinases (BY-kinases) are known to regulate different aspects of bacterial physiology, by phosphorylating cellular protein substrates. Physiological cues that trigger BY-kinases activity are largely unexplored. In Proteobacteria, BY-kinases contain a cytosol-exposed catalytic domain and a…
Matthew Ginley-Hidinger, Julia B. Carleton, Adriana C. Rodriguez, Kristofer C. Berrett + 1 more
Multiple regulatory regions bound by the same transcription factor have been shown to simultaneously control a single gene’s expression. However, it remains unclear how these regulatory regions combine to regulate transcription. Here we test the sufficiency of promoter-distal estrogen receptor α (ER)-binding sites…
Matthew Ginley-Hidinger, Julia B Carleton, Adriana C Rodriguez, Kristofer C Berrett + 1 more
'Kristofer C Berrett' 'Jason Gertz'] Enhancers bound by synthetic activators can recreate a transcriptional response to estrogen, drive different levels of gene expression, and work independently to regulate transcription.
A. I. Curatolo, N. Zhou, Y. Zhao, C. Liu + 3 more
Self-organization is a hallmark of all living systems [1]. In particular, coordinated cellular behavior, commonly orchestrated at the population level through reciprocal interactions among different cell species [2–4], regulates the spatial arrangement of specialized cell types to generate tissue patterning and form…
Ammar Tareen, Ned S. Wingreen, Ranjan Mukhopadhyay
Are "turn-on" and "turn-off" functions in protein-protein interaction networks exact opposites of each other? To answer this question, we implement a minimal model for the evolution of functional protein-interaction networks using a sequence-based mutational algorithm, and apply the model to study neutral drift in…
Authors not listed
Activation of rac-Me2Si(η5-Ind)2ZrMe2 (SBIZrMe2) and sheet models for MAO, (MeAlO)6(Me3Al)4 (6,4), (MeAlO)7(Me3Al)5 (7,5), and (MeAlO)26(Me3Al)9 (26,9) has been studied by DFT. These activators can reversibly form an outer-sphere ion-pair (OSIP) [SBIZrMe2AlMe2] [(MeAlO)n(Me3Al)mMe] 3 ([n,m]− = [7,4]−and [26,8]−) or a…
Célina Reverdy, Gaetan Gitton, Xiangying Guan, Indranil Adhya + 6 more
Among the sirtuin enzymes, Sirt3 is one of the most important deacetylases as it regulates acetylation levels in mitochondria, which are linked to the metabolism of multiple organs and therefore involved in many types of age-related human diseases such as cancer, heart diseases and metabolic diseases. Given the dearth…
Bailey A. Plaman, Wai Cheung Chan, Anthony C. Bishop
Strategies for the direct chemical activation of specific signaling proteins could provide powerful tools for interrogating cellular signal transduction. However, targeted protein activation is chemically challenging, and few broadly applicable activation strategies for signaling enzymes have been developed. Here we…
Shirin Manshouri, Farhad Seif, Monireh Kamali, Mohammad Ali Bahar + 2 more
'Arshideh Mashayekh' 'Rasol Molatefi'] Inflammasomes are complex platforms for the cleavage and release of inactivated IL-1β and IL-18 cytokines that trigger inflammatory responses against damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs). Gut microbiota plays a pivotal role…
Trezze P. Nguyen, Shangze Lyu, Yang Liu
AMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism and other cellular processes. Substantial efforts have been made to develop pharmacological modulators of AMPK activity due to their therapeutic potential against…
Mariya L. Ivanova, Nicola Russo, Gueorgui Mihaylov, Konstantin Nikolić
The study expands the application of scikit-learn-based machine learning (ML) to the prediction of small biomolecule functionalities based on Carbon 13 isotope (13C) NMR spectroscopy data derived from Simplified Molecular Input Line Entry System (SMILES) notations. The methodology previously demonstrated by predicting…
Authors not listed
5’-Adenosine monophosphate-activated protein kinase (AMPK) plays a critical role in maintaining cellular energy homeostasis, and its activation has garnered attention for treating chronic metabolic diseases. Inhibitors of AMPK are underdeveloped but bear implications in treating cancers, controlling autophagy, and…
Sabine Willems, Romy Busch, Felix Nawa, Marco Ballarotto + 12 more
Nuclear receptor related 1 (Nurr1, NR4A2) is a ligand-sensing transcription factor with neuroprotective and anti-inflammatory roles widely distributed in the CNS. Pharmacological Nurr1 modulation is considered a promising experimental strategy in Parkinson's and Alzheimer's disease but target validation is incomplete.…
Irene M. Stoutland, Susan A. Walker, Helen E. Blackwell
Many common bacteria use quorum sensing to regulate cell density-dependent phenotypes, including luminescence, biofilm formation, virulence, and symbiosis. The LuxI/R system is the best-characterized quorum sensing pathway in Gram-negative bacteria and consists of a LuxI-type synthase that produces an N-acyl…
Chris Zhang, Mary Pitman, Anjali Dixit, Sumudu Leelananda + 7 more
DNA-encoded libraries (DELs) provide the means to make and screen millions of diverse compounds against a target of interest in a single experiment. However, despite producing large volumes of binding data at a relatively low cost, the DEL selection process is susceptible to noise, necessitating computational follow-up…
Xiaoqiao Chen, Sisi Chen, Matt Thomson
Sequencing costs currently prohibit the application of single-cell mRNA-seq to many biological and clinical analyses. Targeted single-cell mRNA-sequencing reduces sequencing costs by profiling reduced gene sets that capture biological information with a minimal number of genes. Here, we introduce an active learning…
Authors not listed
Proteolysis targeting chimeras (PROTACs) have helped to establish proximity induction as an exciting strategy in drug discovery, and there are multiple clinical trials focused on this modality. However, degradation of a full protein in a physiological setting might lead to dose-limiting toxicities, giving rise to the…