Objective: To determine the gene regulation of androgen receptor (AR).
Methods: Gel shift assay, protein-protein pull down assay, western blot and technique of site-directed mutagenesis were used to study the gene regulation of AR.
Results: The N terminal of AR contained an inhibitory domain located in an 81-amino acid segment lying upstream of the DNA-binding domain (DBD). The inhibitory domain interacted directly with DBD and repressed DBD binding to the ARE. Mutations of the conserved amino acid residues (K520E and R538E) within the inhibitory domain decreased its inhibiting ability in vitro and increased AR trans-activation in vivo.
Conclusion: These data demonstrated the existence of a novel inhibitory domain in the N-terminal part of AR, which might play important role in the regulation of AR trans-activation.
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Unlabelled: SHP1 (PTPN6) and SHP2 (PTPN11) are closely related protein-tyrosine phosphatases (PTPs), which are autoinhibited until their SH2 domains bind paired tyrosine-phosphorylated immunoreceptor tyrosine-based inhibitory/switch motifs (ITIMs/ITSMs). These PTPs bind overlapping sets of ITIM/ITSM-bearing proteins, suggesting that they might have some redundant functions. By studying T cell-specific single and double knockout mice, we found that SHP1 and SHP2 redundantly restrain naïve T cell differentiation to effector and central memory phenotypes, with SHP1 playing the dominant role.
View Article and Find Full Text PDFEuroasian J Hepatogastroenterol
December 2024
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
Objectives: To predict and characterize the three-dimensional (3D) structure of protein arginine methyltransferase 2 (PRMT2) using homology modeling, besides, the identification of potent inhibitors for enhanced comprehension of the biological function of this protein arginine methyltransferase (PRMT) family protein in carcinogenesis.
Materials And Methods: An method was employed to predict and characterize the three-dimensional structure. The bulk of PRMTs in the PDB shares just a structurally conserved catalytic core domain.
Cell Death Discov
January 2025
The Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Lin28 is a key regulator of cancer stem cell gene network that promotes therapy-resistant tumor progression in various tumors. However, no Lin28 inhibitor has been approved to treat cancer patients, urging exploration of novel compounds as candidates to be tested for clinical trials. In this contribution, we applied computer-aided drug design (CADD) in combination with quantitative biochemical and biological assays.
View Article and Find Full Text PDFZhongguo Fei Ai Za Zhi
November 2024
Yangtze Delta Drug Advanced Research Institute, Nantong 226133, China.
Background: Mutations in the structural domain of the epidermal growth factor receptor (EGFR) kinase represent a critical pathogenetic factor in non-small cell lung cancer (NSCLC). Small-molecule EGFR-tyrosine kinase inhibitors (TKIs) serve as first-line therapeutic agents for the treatment of EGFR-mutated NSCLC. But the resistance mutations of EGFR restrict the clinical application of EGFR-TKIs.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
School of Basic Medical Sciences, Kunming Medical University, Kunming 650500, Yunnan, China. Electronic address:
Most Kunitz inhibitors exhibit serine protease inhibitory activity, but limited information is available on the regulation of platelet function. Herein, we report the purification and characterization of a novel single Kunitz domain inhibitor (Sibanin) from the salivary glands of the black fly Simulium bannaense. Recombinant Sibanin prolonged activated partial thromboplastin time and prothrombin time, and exhibited high-affinity binding to FXa and elastase with a KD of 5.
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