The gene encoding the calcitonin receptor (CTR) was isolated from a porcine kidney epithelial cell line (LLC-PK1) genomic library and found to span approximately 70 kilobases. Analysis of the gene sequence revealed that the CTR mRNA encompasses 14 exons with 12 exons encoding the protein. Two splicing acceptor sites separated by 48 nucleotides were found in intron 7. The expression of two mRNA species in LLC-PK1 cells was subsequently confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and DNA sequencing. In LLC-PK1 cells the mRNA encoding the shorter CTR (CTR-1a) is approximately 1,000 times more abundant than the longer variant (CTR-1b), as estimated by the competitive RT-PCR. The transcription initiation site of the CTR gene was mapped by primer extension, S1 nuclease, and RT-PCR analysis. The proximal promoter region of 500 base pair is GC-rich (66%) and CpG-rich (CpG/GpC ratio 0.71). Transient transfection of CTR gene promoter-luciferase chimeras in LLC-PK1 cells led to the expression of luciferase activity. The CTR gene was mapped to chromosome band 9q11-q12.
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Biochim Biophys Acta Gen Subj
January 2025
Department of Pharmacology, University of Alberta, Edmonton, Canada. Electronic address:
Protein kinase C (PKC) signalling has been shown to be dysregulated in various cancers including acute lymphoblastic leukemia (ALL). We have previously determined that changes in the expression levels of SLC43A3-encoded equilibrative nucleobase transporter 1 (ENBT1) can significantly alter 6-mercaptopurine (6-MP) toxicity in ALL cells. 6-MP is a common drug used in ALL chemotherapy.
View Article and Find Full Text PDFJ Virol
January 2025
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
Porcine epidemic diarrhea virus (PEDV), as a type of Alphacoronavirus causing acute diarrhea and high death rate among sucking piglets, poses great financial damage to the swine industry. Nevertheless, the molecular mechanism whereby PEDV enters host cells is unclear, limiting the development of PED vaccines and anti-PEDV agents. The present study found that the host protein ribonuclease kappa (RNASEK) was regulated by USF2, a transcription factor, and facilitated the PEDV replication.
View Article and Find Full Text PDFEur J Pharm Sci
January 2025
Centre for Applied Pharmacokinetic Research, University of Manchester, UK.
Access of drugs to the central nervous system is limited by the blood-brain barrier, and this in turn affects drug efficacy/toxicity. To date, most drug discovery optimization paradigms have relied heavily on in vitro transporter assays and preclinical species pharmacokinetic evaluation to provide a qualitative assessment of human brain penetration. Because of the lack of human brain pharmacokinetic data, mechanistic models for preclinical species, combined with in vitro and in silico data, are useful for translation to human.
View Article and Find Full Text PDFCell Insight
February 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Medical Research Institute, Wuhan University, Wuhan, 430071, China.
Tumor suppressor protein Adenomatous polyposis coli protein (APC) is an EB-binding and microtubule (MT) plus end-tracking protein; however, how exactly APC regulates MT dynamics remains elusive. Here, we show that in LLC-PK1 cells, APC and KIF2A, an MT depolymerase, form a complex clustering at the cell edge and destabilize MTs at the MT plus ends. Further biochemical characterization and mutational analysis reveal key residues for the APC-KIF2A interaction.
View Article and Find Full Text PDFVirus Res
December 2024
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou University, Yangzhou 225009, PR China. Electronic address:
Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus that poses a serious threat to the global pig industry. Despite extensive efforts, the mechanism underlying virus entry for PEDV remains elusive. In this study, we first identified PEDV-susceptible and non-susceptible cell lines by using PEDV spike pseudotyped vesicular stomatitis virus.
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