Because of the pivotal role of mitochondrial alterations in several diseases, the Human Proteome Organization (HUPO) has promoted in recent years an initiative to characterize the mitochondrial human proteome, the mitochondrial human proteome project (mt-HPP). Here we generated an updated version of the functional mitochondrial human proteome network, made by nodes (mitochondrial proteins) and edges (gold binary interactions), using data retrieved from neXtProt, the reference database for HPP metrics. The principal new concept suggested was the consideration of mitochondria-associated proteins (first interactors), which may influence mitochondrial functions. All of the proteins described as mitochondrial in the sublocation or the GO Cellular Component sections of neXtProt were considered. Their other subcellular and submitochondrial localizations have been analyzed. The network represents the effort to collect all of the high-quality binary interactions described so far for mitochondrial proteins and the possibility for the community to reuse the information collected. As a proof of principle, we mapped proteins with no function, to speculate on their role by the background knowledge of their interactors, and proteins described to be involved in Parkinson's Disease, a neurodegenerative disorder, where it is known that mitochondria play a central role.
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http://dx.doi.org/10.1021/acs.jproteome.8b00447 | DOI Listing |
Chembiochem
January 2025
University of Konstanz, Department of Chemistry, Universitaetsstrasse 10, 78457, Konstanz, GERMANY.
The ubiquitin (Ub) ligase E6AP, which is encoded by the UBE3A gene, has been associated with several human diseases including cervical cancer and Angelman syndrome, a neurodevelopmental disorder. Yet, our knowledge about disease-relevant substrates of E6AP is still limited. The formation of a thioester complex between Ub and the catalytic Cys residue of E6AP represents an essential intermediate step in E6AP-mediated ubiquitination.
View Article and Find Full Text PDFGenes Dev
December 2024
Institute for Diabetes, Obesity, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19146, USA;
The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific deletion mouse strain ( ) and found that is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux.
View Article and Find Full Text PDFCancer Biol Ther
December 2025
State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, Air Force Military Medical University, Xi'an, China.
Ribosomal S6 protein kinase 4 (RSK4), a member of the serine‒threonine kinase family, plays a vital role in the Ras‒MAPK pathway. This kinase is responsible for managing several cellular activities, including cell growth, proliferation, survival, and mobility. In this study, we observed higher RSK4 protein expression in clear cell renal cell carcinoma (ccRCC) than in normal kidney tissue, and the overexpression of RSK4 might predict poor outcomes for ccRCC patients.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis School of Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA.
Patient-centered precision oncology strives to deliver individualized cancer care. In lung cancer, preclinical models and technological innovations have become critical in advancing this approach. Preclinical models enable deeper insights into tumor biology and enhance the selection of appropriate systemic therapies across chemotherapy, targeted therapies, immunotherapies, antibody-drug conjugates, and emerging investigational treatments.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan.
Recently, we demonstrated that the alopecia observed in vitamin D receptor gene-deficient (-KO) rats is not seen in rats with a mutant VDR(R270L/H301Q), which lacks ligand-binding ability, suggesting that the ligand-independent action of VDR plays a crucial role in maintaining the hair cycle. Since -KO rats also showed abnormalities in the skin, the relationship between alopecia and skin abnormalities was examined. To clarify the mechanism of actions of vitamin D and VDR in the skin, protein composition, and gene expression patterns in the skin were compared among -KO, -R270L/H301Q, and wild-type (WT) rats.
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