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J Proteomics 2021 Apr 10:104197. Epub 2021 Apr 10.

Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA 91125, USA. Electronic address:

Proteasome inhibitors are an important class of chemotherapeutic drugs. In this study, we performed a large-scale ubiquitylome analysis of the three proteasome inhibitors MG132, bortezomib and carfilzomib. Although carfilzomib is currently being used for the treatment of multiple myeloma, it has not yet been subjected to a global ubiquitylome analysis. Read More

J Phys Chem B 2021 Apr 9. Epub 2021 Apr 9.

Laboratory of Protein Conformation and Dynamics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.

Aggregated TAR DNA-binding protein 43 (TDP-43) forms the cytoplasmic hallmarks associated with patients suffering from amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin. Under normal conditions, TDP-43 is a 414-amino acid protein; however, aggregates are enriched with N-terminal truncations which contain residues 267-414, known as the C-terminal domain of TDP-43 (TDP-43). To gain residue-specific information on the aggregation process of TDP-43, we created three single-Trp containing mutants (W385F/W412F, W334F/W412F, and W334F/W385F) by substituting two of the three native Trp residues with Phe, yielding fluorescent probes at W334, W385, and W412, respectively. Read More

Sci Adv 2021 Apr 7;7(15). Epub 2021 Apr 7.

Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

The serine/threonine kinase ULK1 mediates autophagy initiation in response to various cellular stresses, and genetic deletion of ULK1 leads to accumulation of damaged mitochondria. Here we identify Parkin, the core ubiquitin ligase in mitophagy, and PARK2 gene product mutated in familial Parkinson's disease, as a ULK1 substrate. Recent studies uncovered a nine residue ("ACT") domain important for Parkin activation, and we demonstrate that AMPK-dependent ULK1 rapidly phosphorylates conserved serine108 in the ACT domain in response to mitochondrial stress. Read More

Int J Mol Sci 2021 Mar 22;22(6). Epub 2021 Mar 22.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, College of Agriculture, Guangxi University, Nanning 530004, China.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas9)-mediated genome editing has become an important way for molecular breeding in crop plants. To promote rice breeding, we edited the () gene for obtaining valuable and stable long-grain rice mutants. Furthermore, isobaric tags for the relative and absolute quantitation (iTRAQ)-based proteomic method were applied to determine the proteome-wide changes in the mutants compared with wild type (WT). Read More