Human securin (PTTG1) is a protooncogene whose expression is elevated in many types of malignant cells. We previously discovered a minor short isoform of securin lacking exons 3 and 4. The missing exons encode the main recognition site (D-box) of the anaphase-promoting complex (APC/C). We show that these two PTTG1 isoforms have different effects on transcription. Here, we have studied the effects of overexpression and selective knockdown of the short and complete securin isoforms on cell proliferation using the xCELLigence system. Notably, selective knockdown of the short isoform mRNA led to a dramatic decrease in cell growth, while overexpression of both isoforms accelerated cell growth. To search for genes with alternative isoforms similar to securin, we analyzed the GENCODE database and found that 54 of 128 genes with a PTTG1-like set of APC/C recognition sites have known isoforms without the D-box. Overall, the data obtained indicate the existence of a new class of alternative isoforms and reinstates the importance of minor isoforms.
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http://dx.doi.org/10.31857/S0026898422060076 | DOI Listing |
Adv Biotechnol (Singap)
February 2024
National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang, China.
Alternative splicing (AS) significantly enriches the diversity of transcriptomes and proteomes, playing a pivotal role in the physiology and development of eukaryotic organisms. With the continuous advancement of high-throughput sequencing technologies, an increasing number of novel transcript isoforms, along with factors related to splicing and their associated functions, are being unveiled. In this review, we succinctly summarize and compare the different splicing mechanisms across prokaryotes and eukaryotes.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Department of Biology, Adelphi University, One South Avenue, P.O. Box 701, Garden City, NY, 11530-0701, USA.
Background: von Hippel-Lindau (VHL) hereditary cancer syndrome is caused by mutations in the VHL tumor suppressor gene and is characterized by a predisposition to form various types of tumors, including renal cell carcinomas, hemangioblastomas, and pheochromocytomas. The protein products of the VHL gene, pVHL, are part of an ubiquitin ligase complex that tags hypoxia inducible factor alpha (HIF-α) for proteosomal degradation. pVHL has also been reported to bind to atypical protein kinase C (aPKC).
View Article and Find Full Text PDFMol Biol Rep
January 2025
Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability Center, 713-8 Kamiya, Kasugai, 486-0392, Japan.
Background: RAB11 is a small GTP-binding protein that regulates intracellular trafficking of recycling endosomes and is thereby involved in several neural functions. Highly similar RAB11 isoforms are encoded by RAB11A and RAB11B genes, and their pathogenic variants are associated with similar neurodevelopmental disorders, suggesting that RAB11A and RAB11B play similar and important roles in brain development. However, the detailed distribution patterns of these isoforms in various organs, including the brain, remain undetermined.
View Article and Find Full Text PDFIUCrJ
March 2025
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 02-093 Warsaw, Poland.
Quantum crystallography methods have been employed to investigate complex formation between nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) enzymes, with particular focus on the COX-1 and COX-2 isoforms. This study analyzed the electrostatic interaction energies of selected NSAIDs (flurbiprofen, ibuprofen, meloxicam and celecoxib) with the active sites of COX-1 and COX-2, revealing significant differences in binding profiles. Flurbiprofen exhibited the strongest interactions with both COX-1 and COX-2, indicating its potent binding affinity.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya, Japan.
The high interstitial ATP concentration in the cancer microenvironment is a major source of adenosine, which acts as a strong immune suppressor. However, the source of ATP release has not been elucidated. We measured ATP release during hypotonic stress using a real-time ATP luminescence imaging system in breast cell lines and in primary cultured mammary cells.
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