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| Open AccessLarge-scale plasma proteomics comparisons through genetics and disease associations
Comparisons of phenotypic and genetic association with protein levels from Icelandic and UK Biobank cohorts show that using multiple analysis platforms and stratifying populations by ancestry improves the detection of associations and allows the refinement of their location within the genome.
- Grimur Hjorleifsson Eldjarn
- , Egil Ferkingstad
- & Kari Stefansson
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Article
| Open AccessProteome census upon nutrient stress reveals Golgiphagy membrane receptors
A proteomics analysis demonstrates that, during nutrient stress, mammalian cells prioritize degradation by autophagy of membrane proteins and identifies receptors that mediate this process at the Golgi and also have a role in Golgi remodelling during neuronal differentiation.
- Kelsey L. Hickey
- , Sharan Swarup
- & J. Wade Harper
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Article
| Open AccessAstrocyte–neuron subproteomes and obsessive–compulsive disorder mechanisms
Analyses of the proteomes of astrocytes and neurons in a cell-specific and subcompartment-specific manner reveal distinct roles for these cell types that are relevant to obsessive–compulsive disorder and perhaps other brain disorders.
- Joselyn S. Soto
- , Yasaman Jami-Alahmadi
- & Baljit S. Khakh
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Systems-level effects of allosteric perturbations to a model molecular switch
Interface mutations in the GTPase switch protein Gsp1 (the yeast homologue of human RAN) allosterically affect the kinetics of the switch cycle, revealing a systems-level mechanism of multi-specificity.
- Tina Perica
- , Christopher J. P. Mathy
- & Tanja Kortemme
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Article
| Open AccessHighly accurate protein structure prediction for the human proteome
AlphaFold is used to predict the structures of almost all of the proteins in the human proteome—the availability of high-confidence predicted structures could enable new avenues of investigation from a structural perspective.
- Kathryn Tunyasuvunakool
- , Jonas Adler
- & Demis Hassabis
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Article |
Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms
Inhibition of YBX1, a downstream target of the Janus kinase JAK2, sensitizes myeloproliferative neoplasm cells to JAK and could provide a means to eradicate such cells in human haematopoietic cancers.
- Ashok Kumar Jayavelu
- , Tina M. Schnöder
- & Florian H. Heidel
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Article |
Light-driven post-translational installation of reactive protein side chains
A wide range of side chains are installed into proteins by addition of photogenerated alkyl or difluroalkyl radicals, providing access to new functionality and reactivity in proteins.
- Brian Josephson
- , Charlie Fehl
- & Benjamin G. Davis
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Article |
The dental proteome of Homo antecessor
Analyses of the proteomes of dental enamel from Homo antecessor and Homo erectus demonstrate that the Early Pleistocene H. antecessor is a close sister lineage of later Homo sapiens, Neanderthal and Denisovan populations in Eurasia.
- Frido Welker
- , Jazmín Ramos-Madrigal
- & Enrico Cappellini
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Mass-spectrometry-based draft of the Arabidopsis proteome
A quantitative atlas of the transcriptomes, proteomes and phosphoproteomes of 30 tissues of the model plant Arabidopsis thaliana provides a valuable resource for plant research.
- Julia Mergner
- , Martin Frejno
- & Bernhard Kuster
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Letter |
Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts
The authors find that stromal methyltransferase nicotinamide N-methyltransferase (NNMT) regulates the transition of normal fibroblasts to cancer-associated fibroblasts through histone methylation and promotes ovarian cancer growth and metastasis.
- Mark A. Eckert
- , Fabian Coscia
- & Ernst Lengyel
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Letter |
BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation
The mechanistic basis for the role of the metabolic enzyme BCAA transaminase 1 (BCAT1) in acute myeloid leukaemias.
- Simon Raffel
- , Mattia Falcone
- & Andreas Trumpp
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Letter |
Comparative glycoproteomics of stem cells identifies new players in ricin toxicity
A novel quantitative approach to identify intact glycopeptides from comparative proteomic data sets, allowing inference of complex glycan structures and direct mapping of them to sites within the associated proteins at the proteome scale.
- Johannes Stadlmann
- , Jasmin Taubenschmid
- & Josef M. Penninger
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Article |
Proteogenomics connects somatic mutations to signalling in breast cancer
Quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of genomically annotated human breast cancer samples elucidates functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies potential therapeutic targets.
- Philipp Mertins
- , D. R. Mani
- & Steven A. Carr
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Article |
∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis
A new deep proteomic analysis method is used to identify proteins that interact with wild-type cystic fibrosis transmembrane conductance regulator (CFTR) and its mutant version that is the major cause of cystic fibrosis.
- Sandra Pankow
- , Casimir Bamberger
- & John R. Yates III
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Letter |
Multiplex single-molecule interaction profiling of DNA-barcoded proteins
Single-molecular-interaction-sequencing involves attaching DNA barcodes to proteins, assaying these barcoded proteins en masse in an aqueous solution, followed by immobilization in a polyacrylamide film and amplifying and analysing the barcoding DNAs—the method allows for precise protein quantification and simultaneous interrogation of molecular binding affinity and specificity.
- Liangcai Gu
- , Chao Li
- & George M. Church
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Article |
Proteogenomic characterization of human colon and rectal cancer
Proteome analysis of The Cancer Genome Atlas (TCGA) colorectal cancer specimens reveals that DNA- or RNA-level measurements cannot reliably predict protein abundance, colorectal tumours can be separated into distinct proteotypes, and that copy number alterations drive mRNA abundance changes but few extend to protein-level changes.
- Bing Zhang
- , Jing Wang
- & R. Reid Townsend
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Article |
A draft map of the human proteome
A draft map of the human proteome is presented here, accounting for over 80% of the annotated protein-coding genes in humans; some novel protein-coding regions, including translated pseudogenes, non-coding RNAs and upstream open reading frames, are identified.
- Min-Sik Kim
- , Sneha M. Pinto
- & Akhilesh Pandey
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Letter |
Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy
Through a quantitative proteomics analysis, a cohort of proteins is identified that associate with autophagosomes, among them a new cargo receptor called NCOA4 that, in response to iron deprivation, targets ferritin to autophagosomes and thereby releases iron.
- Joseph D. Mancias
- , Xiaoxu Wang
- & Alec C. Kimmelman
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Letter |
A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers
- Siwanon Jirawatnotai
- , Yiduo Hu
- & Piotr Sicinski
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News & Views |
Snapshot of the network
Autophagy is an essential cellular process for protein and organelle quality control. Analyses of proteins that interact with the human autophagic machinery provide an outline of the molecular organization of this pathway.
- Beth Levine
- & Rama Ranganathan
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Letter |
Transcriptional role of cyclin D1 in development revealed by a genetic–proteomic screen
Although cyclin D1 is frequently overexpressed in human cancers, the full range of its functions in normal development and oncogenesis is unclear. Here, tagged cyclin D1 knock-in mouse strains are developed to allow a search for cyclin D1-binding proteins in different mouse organs using high-throughput mass spectrometry. The results show that, in addition to its established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development.
- Frédéric Bienvenu
- , Siwanon Jirawatnotai
- & Piotr Sicinski