Results 41 to 50 of about 419,478 (257)

Phosphatidylinositol 4‐kinase as a target of pathogens—friend or foe?

FEBS Letters, EarlyView.
This graphical summary illustrates the roles of phosphatidylinositol 4‐kinases (PI4Ks). PI4Ks regulate key cellular processes and can be hijacked by pathogens, such as viruses, bacteria and parasites, to support their intracellular replication. Their dual role as essential host enzymes and pathogen cofactors makes them promising drug targets.
Ana C. Mendes, Guilherme M. Azevedo, Amanda P. Barcellos, Diana Bahia   +3 more
wiley   +1 more source

Molecular bases of circadian magnesium rhythms across eukaryotes

FEBS Letters, EarlyView.
Circadian rhythms in intracellular [Mg2+] exist across eukaryotic kingdoms. Central roles for Mg2+ in metabolism suggest that Mg2+ rhythms could regulate daily cellular energy and metabolism. In this Perspective paper, we propose that ancestral prokaryotic transport proteins could be responsible for mediating Mg2+ rhythms and posit a feedback model ...
Helen K. Feord, Gerben van Ooijen
wiley   +1 more source

Discovery of a CNS active GSK3 degrader using orthogonally reactive linker screening

Nature Communications
Bifunctional targeted protein degraders, also known as Proteolysis Targeting Chimeras (PROTACs), are an emerging drug modality that may offer a new approach for treating neurodegenerative diseases. Identifying chemical starting points for PROTACs remains
Andreas Holmqvist, Nur Mehpare Kocaturk, Christina Duncan, Jennifer Riley, Steven Baginski, Graham Marsh, Joel Cresser-Brown, Hannah Maple, Kristiina Juvonen, Gajanan Sathe, Nicola Morrice, Calum Sutherland, Kevin D. Read, William Farnaby   +13 more
doaj   +1 more source

Crosstalk between the ribosome quality control‐associated E3 ubiquitin ligases LTN1 and RNF10

FEBS Letters, EarlyView.
Loss of the E3 ligase LTN1, the ubiquitin‐like modifier UFM1, or the deubiquitinating enzyme UFSP2 disrupts endoplasmic reticulum–ribosome quality control (ER‐RQC), a pathway that removes stalled ribosomes and faulty proteins. This disruption may trigger a compensatory response to ER‐RQC defects, including increased expression of the E3 ligase RNF10 ...
Yuxi Huang, Satoshi Hashimoto, Sota Ito, Chisato Kikuguchi, Miho Hoshi, Kiyoshi Yamaguchi, Yoichi Furukawa, Toru Suzuki, Toshifumi Inada   +8 more
wiley   +1 more source

Combination of AID2 and BromoTag expands the utility of degron-based protein knockdowns

EMBO Reports
Acute protein knockdown is a powerful approach to dissecting protein function in dynamic cellular processes. We previously reported an improved auxin-inducible degron system, AID2, but recently noted that its ability to induce degradation of some ...
Yuki Hatoyama, Moutushi Islam, Adam G Bond, Ken-ichiro Hayashi, Alessio Ciulli, Masato T Kanemaki   +5 more
doaj   +1 more source

Interplay between circadian and other transcription factors—Implications for cycling transcriptome reprogramming

FEBS Letters, EarlyView.
This perspective highlights emerging insights into how the circadian transcription factor CLOCK:BMAL1 regulates chromatin architecture, cooperates with other transcription factors, and coordinates enhancer dynamics. We propose an updated framework for how circadian transcription factors operate within dynamic and multifactorial chromatin landscapes ...
Xinyu Y. Nie, Jerome S. Menet
wiley   +1 more source

Macrocycle-based PROTACs selectively degrade cyclophilin A and inhibit HIV-1 and HCV

Nature Communications
Targeting host proteins that are crucial for viral replication offers a promising antiviral strategy. We have designed and characterised antiviral PROteolysis TArgeting Chimeras (PROTACs) targeting the human protein cyclophilin A (CypA), a host cofactor ...
Lydia S. Newton, Clara Gathmann, Sophie Ridewood, Robert J. Smith, Andre J. Wijaya, Thomas W. Hornsby, Kate L. Morling, Dara Annett, Riccardo Zenezini Chiozzi, Ann-Kathrin Reuschl, Morten L. Govasli, Ying Ying Tan, Lucy G. Thorne, Clare Jolly, Konstantinos Thalassinos, Alessio Ciulli, Greg J. Towers, David L. Selwood   +17 more
doaj   +1 more source

Targeted protein degradation and drug discovery

The Journal of Biochemistry, 2022
Abstract Targeted protein degradation attracts attention as a novel modality for drug discovery, as well as for basic research. Various types of degrader molecules have been developed so far, which include proteolysis-targeting chimaeras (PROTACs) and specific and nongenetic IAP-dependent protein erasers (SNIPERs), E3 modulators ...
openaire   +2 more sources

Disordered but rhythmic—the role of intrinsic protein disorder in eukaryotic circadian timing

FEBS Letters, EarlyView.
Unstructured domains known as intrinsically disordered regions (IDRs) are present in nearly every part of the eukaryotic core circadian oscillator. IDRs enable many diverse inter‐ and intramolecular interactions that support clock function. IDR conformations are highly tunable by post‐translational modifications and environmental conditions, which ...
Emery T. Usher, Jacqueline F. Pelham
wiley   +1 more source

The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system

Nature Communications, 2022
Targeted protein degradation is a promising approach for basic research and therapeutic applications. Here, the authors develop a targeted protein degradation platform called AUTOTAC to degrade oncoproteins and neurodegeneration-associated proteins via ...
Chang Hoon Ji, Hee Yeon Kim, Min Ju Lee, Ah Jung Heo, Daniel Youngjae Park, Sungsu Lim, Seulgi Shin, Woo Seung Yang, Chang An Jung, Kun Young Kim, Eun Hye Jeong, Sun Ho Park, Su Bin Kim, Su Jin Lee, Jeong Eun Na, Ji In Kang, Hyung Min Chi, Hyun Tae Kim, Yun Kyung Kim, Bo Yeon Kim, Yong Tae Kwon   +20 more
doaj   +1 more source