Marked for destruction
The significance of the first FDA-approved PROTAC lies not in proving that targeted protein degradation is superior to conventional therapies, but in proving that degrading proteins is possible as a therapeutic go.nature.com/4x3NYt7
Could the #ribosome be a selfish element? @mkrupovic.bsky.social & Eugene Koonin propose that the #evolution of life can viewed as a ribosomal takeover, where the ribosome evolved to consume most of the cell’s resources.
🧪 #OriginsOfLife
Nature Biotechnology
In this Essay, the evolution of life is construed as a ribosomal takeover, whereby the ribosome evolved to consume most of the cell’s resources, while other cellular componentry ensured the…
We identify novel catalytically impaired PARP1 mutants and show that the toxicity of some variants in cells can be rescued by the PARP inhibitor saruparib. Thus, in specific contexts, saruparib plays a pro-survival role rather than a cytotoxic one.
www.cell.com/cell-reports...
Noboru Mizushima is Professor of Biochemistry and Molecular Biology at the University of Tokyo, Japan, where he runs a laboratory studying the mechanisms and physiological functions of autophagy and o...
Everything you wanted to know about the protein chemistry behind how amino-acid changes affect the cellular abundance of proteins from @tkschulze.bsky.social
Effects of residue substitutions on the cellular abundance of proteins
doi.org/10.7554/eLif...
Our paper is now out in @natcellbio.nature.com! @craigmcrews.bsky.social
www.nature.com/articles/s41...
We identify a new regulator of the quality control system that protects one of nature's most important molecular machines: the ribosome. QC failure → unmitigated metabolic stress & cell death.
Schützenhofer et al. show that expression of catalytically impaired PARP1 mutants
is toxic to cells, which can be overcome by treatment with saruparib, a PARP1-specific
inhibitor that displays a pro-r...
www.cell.com
Very interesting articles about cancer metabolism this month, and insightful reviews.
Highlighting fresh articles and comments about cysteine and glutathione from @lucasbsullivan.bsky.social @ginadenicola.bsky.social @harrislab.bsky.social and others
metabolist.wordpress.com/2026/05/04/m...
Douglas et al. study the E3 ligase HOIL-1, mutated in patients with a type of myopathy. Mutant HOIL-1 influences the sensitivity to disulfidptosis initiated by ZAKα–ATF4 in glucose starvation and inte...
Cystine / Glutathione / NADPH SLC33A1 exports oxidized glutathione to maintain endoplasmic reticulum redox homeostasis Shanshan Liu (刘珊珊), Mark Gad, Caifan Li (李采蘩), Kevin Cho, Yuyang Liu (刘雨洋),…
metabolist.wordpress.com
Isabel
Todd Douglas
Excited to finally share our preprint on mapping the genetic interaction network of the DNA damage response with combinatorial knockout screens led by Sam Hayward, Alina Vaitsiankova, and Tomas Lama-Diaz! www.biorxiv.org/cgi/content/...
Doing the periodic cleaning of used plasmid miniprep columns and realized in honor of Earth Day it may be worth reminding you molecular biologists:
Plasmid miniprep columns can be cleaned and reused essentially indefinitely! Just add 1 M HCl, soak overnight and wash 3x w/ water. Save $ and plastic
Kresten Lindorff-Larsen
Cristina Muñoz Pinedo
The DNA damage response (DDR) is a complex network of cellular pathways that ensures the faithful maintenance of our genomes upon a wide array of genomic insults. To elucidate the functional architect...
