The proline-rich inhibitor of 31 kDa (PI31) is highly conserved through metazoan evolution, and its activity in the proteasome inhibition is well-established although the precise mechanism of inhibition is unclear. The coding DNA sequence of Schistosoma mansoni PI31 (SmPI31) was cloned, and the recombinant protein was expressed in bacterial system. The correct amino acid sequence was confirmed by mass spectrometry and circular dichroism suggests that SmPI31 contains both α-helix and non-structured regions. Inhibition assays, using the Suc-Leu-Leu-Val-Tyr-4-MCA substrate for proteasome degradation, showed that the S. mansoni proteasome may be regulated by the inhibitory activity of SmPI31. A gene expression assay using qRT-PCR at various stages during the S. mansoni life cycle has shown that SmPI31 transcripts are expressed in all studied stages, suggesting that PI31 plays an important role during the developmental processes of the parasite. In this study first evidence is presented that PI31 has a conserved structure and plays a role as proteasome inhibitor in adult worms and it is expressed through life cycle.
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http://dx.doi.org/10.1007/s00436-010-1984-x | DOI Listing |
Nat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
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January 2025
Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041 Sichuan Province, People's Republic of China. Electronic address:
Chimeric antigen receptor T (CAR-T) cell therapy targeting B cell mature antigen (BCMA) has shown remarkable clinical benefits in treating multiple myeloma (MM). Bortezomib, a proteasome inhibitor approved as a first-line agent for MM for two decades, has demonstrated potent antitumor activity. In this study, we found that bortezomib treatment stabilizes the expression of BCMA and conceived the hypothesis that BCMA CAR-T therapy combined with bortezomib would enhance the anti-MM efficacy.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, 41013 Seville, Spain.
The ubiquitin proteasome system (UPS) is implicated in protein homeostasis. One of the proteins involved in this system is HERC1 E3 ubiquitin ligase, which was associated with several processes including the normal development and neurotransmission at the neuromuscular junction (NMJ), autophagy in projection neurons, myelination of the peripheral nervous system, among others. The tambaleante (tbl) mouse model carries the spontaneous mutation Gly483Glu substitution in the HERC1 E3 protein.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Ave., MSC509, Charleston, SC 29425, USA.
Cutaneous T-cell lymphoma (CTCL) is a rare T-cell malignancy characterized by inflamed and painful rash-like skin lesions that may affect large portions of the body's surface. Patients experience recurrent infections due to a compromised skin barrier and generalized immunodeficiency resulting from a dominant Th2 immune phenotype of CTCL cells. Given the role of the unfolded protein response (UPR) in normal and malignant T-cell development, we investigated the impact of UPR-inducing drugs on the viability, transcriptional networks, and Th2 phenotype of CTCL.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy.
Algae are a rich source of bioactive compounds that have a wide range of beneficial effects on human health and can show significant potential in the treatment of hematological malignancies such as leukemia, lymphoma, and multiple myeloma. These diseases often pose a therapeutic challenge despite recent advances in treatment (e.g.
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