Results 91 to 100 of about 714,957 (298)

The ubiquitin ligase RNF115 is required for the clearance of damaged lysosomes

FEBS Letters, EarlyView.
Upon lysosomal rupture, an E3 ubiquitin ligase RNF115 translocates from the cytosol to the damaged lysosomal membrane. Moreover, RNF115 depletion impairs the clearance of damaged lysosomes, identifying it as a key regulator of lysosomal quality control.
Sae Nakanaga, Toshiki Takahashi, Akiko Kuma, Hiroyuki Kawahara   +3 more
wiley   +1 more source

Explainable artificial intelligence for targeted protein degradation predictions

Artificial Intelligence in the Life Sciences
Defining structure-activity relationships (SAR) is a central task in medicinal chemistry. Apart from optimizing activity against the target of interest, off-target activities and other properties need to be balanced to ensure a suitable property profile,
Francis J. Prael III, Jutta Blank, William C. Forrester, Lingling Shen, Raquel Rodríguez-Pérez   +4 more
doaj   +1 more source

To translate, or not to translate: viral and host mRNA regulation by interferon-stimulated genes. [PDF]

, 2015
Type I interferon (IFN) is one of the first lines of cellular defense against viral pathogens. As a result of IFN signaling, a wide array of IFN-stimulated gene (ISG) products is upregulated to target different stages of the viral life cycle.
Li, Melody MH, MacDonald, Margaret R, Rice, Charles M   +2 more
core   +1 more source

Targeting the undruggables—the power of protein degraders

Science Bulletin
Undruggable targets typically refer to a class of therapeutic targets that are difficult to target through conventional methods or have not yet been targeted, but are of great clinical significance. According to statistics, over 80% of disease-related pathogenic proteins cannot be targeted by current conventional treatment methods.
Chao, Zhang, Yongbo, Liu, Guangchen, Li, Zhouli, Yang, Chi, Han, Xiuyun, Sun, Chunquan, Sheng, Ke, Ding, Yu, Rao   +8 more
openaire   +2 more sources

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

AAA+ protein unfoldases—the Moirai of the proteome

FEBS Letters, EarlyView.
AAA+ unfoldases are essential molecular motors that power protein degradation and disaggregation. This review integrates recent cryo‐electron microscopy (cryo‐EM) structures and single‐molecule biophysical data to reconcile competing models of substrate translocation.
Stavros Azinas, Marta Carroni
wiley   +1 more source

Traffic into silence: endomembranes and post-transcriptional RNA silencing. [PDF]

, 2014
microRNAs (miRNAs) and small interfering RNAs (siRNAs) are small RNAs that repress gene expression at the post-transcriptional level in plants and animals. Small RNAs guide Argonaute-containing RNA-induced silencing complexes to target RNAs in a sequence-
Chen, Xuemei, Kim, Yun Ju, Maizel, Alexis   +2 more
core   +3 more sources

pH‐mediated activation of the lysosomal arginine sensor SLC38A9

FEBS Letters, EarlyView.
Cells monitor nutrient levels via the lysosomal transporter SLC38A9 to activate the mechanistic target of rapamycin complex 1 (mTORC1). This study reveals that SLC38A9 function is regulated by pH. We identified histidine 544 as a critical pH sensor that undergoes conformational changes to control amino acid efflux from lysosomes; therefore, it ...
Xuelang Mu, Ampon Sae Her, Tamir Gonen
wiley   +1 more source

Intrinsic signaling pathways modulate targeted protein degradation

Nature Communications
Targeted protein degradation is a groundbreaking modality in drug discovery; however, the regulatory mechanisms are still not fully understood. Here, we identify cellular signaling pathways that modulate the targeted degradation of the anticancer target ...
Yuki Mori, Yoshino Akizuki, Rikuto Honda, Miyu Takao, Ayaka Tsuchimoto, Sota Hashimoto, Hiroaki Iio, Masakazu Kato, Ai Kaiho-Soma, Yasushi Saeki, Jun Hamazaki, Shigeo Murata, Toshikazu Ushijima, Naoko Hattori, Fumiaki Ohtake   +14 more
doaj   +1 more source

Targeting of the prion protein to the cytosol: mechanisms and consequences

, 2010
Prion diseases are characterized by the conformational transition of the cellular prion protein (PrPC) into an aberrant protein conformer, designated scrapie-prion protein (PrPSc).
Miesbauer, M., Rambold, A., Tatzelt, J., Winkelhofer, K.   +3 more
core