Project description:To extensively elucidate protein lactylation (Kla), a proteome-wide analysis of lactylation was carried out in Staphylococcus aureus. Proteins extracted from Staphylococcus aureus were digested by trypsin and anti-lactyl lysine antibody was used to enrich the lactylated peptides, which were determined by following LC-MS/MS analysis.
Project description:To understand the symbiotic relationship between the Conchocele bisecta and its bacterial symbiont, the metaproteomic sequencing and anlysis of the symbiotic gill tissue of Conchocele bisecta were conducted.
Project description:To gain insight into the potential cargo proteins mediated by KPNB1, the nuclear fraction of DMSO- and IPZ-treated NB-4 cells were isolated and then subjected to mass spectrometry analysis.
Project description:Clinical resistance such as androgen receptor (AR) mutation, AR overexpression, and AR splice variants (ARVs) restrict the second-generation antiandrogens benefit in patients with castration-resistant prostate cancer (CRPC). Several strategies have been implemented to develop novel antiandrogens to circumvent the occurring resistance. In this study, based on rational drug design, we discovered and identified a bifunctional small molecule Z15 as a potent AR antagonist and AR selective degrader. Z15 could directly bind to the AR ligand-binding domain (LBD) and inhibited DHT-induced AR nuclear translocation. Furthermore, Z15 promoted AR degradation through the proteasome pathway. As a result, our in vitro and in vivo studies showed Z15 efficiently suppressed AR and AR mutant transcription activity, downregulated mRNA and protein levels of AR target genes, as well as overcame AR LBD mutations, AR amplification, and ARVs-induced resistance in CRPC. In conclusion, our data illustrate the synergistic importance of AR antagonism and degradation in advanced prostate cancer treatment.
Project description:Applying 4D-label free method to detect differential proteins in cancer tissue and para-cancerous tissue in 6 patients with hepatocellular carcinoma.
Project description:Differential protein expression in LSCC with negative lymphatic metastasis (LNM-) and LSCC with positive lymphatic metastasis (LNM+) TAMs was subsequently analyzed by 4D label-free proteomics.
Project description:Defective autophagy is linked to proinflammatory diseases. However, the mechanisms by which autophagy limits inflammation remain elusive. Here, we found that the pan-FGFR inhibitor LY2874455 efficiently activated autophagy and suppressed innate inflammation in macrophages stimulated by lipopolysaccharide (LPS). The mass spectrometry-based proteomics analysis of RAW264.7 cells treated with LPS (20ng/ml) and LY2874455 was performed. The protein levels of macrophages were systematically analyzed and quantified. Then, the protein levels were compared. The fold change and significance were analyzed. Multiplex proteomic profiling identified the immunoproteasome, a specific isoform of the 20s constitutive proteasome, as substrates that are degraded by selective autophagy. SQSTM1/p62 was found to be a selective autophagy-related receptor that mediated this degradation. Autophagy deficiency or p62 knockdown blocked the effects of LY2874455, leading to the accumulation of immunoproteasomes and increases in inflammatory reactions.
Project description:Congo Red (CR) dye is historically used for histochemical staining of amyloid deposition in tissue. Its characteristic aryl azo moiety renders it chemically stable as a non-covalent pan-amyloid binder. Here, we discover in serendipity that the CR dye can covalently modify amyloid proteins by activation of the inert azo bond using neutral borate buffer at ambient temperature. We first show that boronic acid is responsible for azo bond-mediated protein bioconjugation. Furthermore, we also observe that ultraviolet light-induced azo trans-to-cis isomerization significantly enhances the labeling efficiency. Leveraging the discovered covalent chemistry, we apply CR-alkyne derivative with a click enrichment handle to label, capture and enrich amyloid deposits in Alzheimer’s disease (AD) mouse brain tissue. Finally, we identify the composition of amyloid deposits by proteomics profiling, revealing typical neurodegenerative diseases biomarkers, including MAPT and 14-3-3 family proteins. Overall, this work presents a new type of azo based bioconjugation chemistry previously known to be inert but herein activated by neutral borate buffer.
Project description:Amyloid protein deposit, like Aβ plaques, is a pathological hallmark of Alzheimer’s disease (AD). While plenty of amyloid imaging reagents available for diagnosis, their composition associated with disease etiology is challenging to analyze in intact tissue sample. Herein, we report an amyloid-targeting probe to photocatalyze in-situ labeling and profiling of Aβ plaques in AD brain tissue via single electron transfer (SET) mechanism. First, we render this amyloid probe with photocatalytic labeling function by fragment fusion of classical scaffolds of fluorescent amyloid sensors. Second, we demonstrate its labeling selectivity to amyloid proteins over monomer counterparts. Mechanistically, we show spatially resolved labeling is driven by the short-lived SET photocatalytic process. Finally, we use this probe to capture and profile the composition of amyloid plagues in Alzheimer’s disease brain tissue. Surpassing other AD proteomics datasets, our work spatially resolves pathogenic Aβ and typical AD biomarkers as top-ranked hits. Together, the short-lived SET-driven photocatalysis spatially restrains protein labeling to occur in ultra-proximity to amyloids, allowing for microscope-free amyloid tissue microdissection at molecular level.
Project description:Endometrial carcinoma (EC) remains a public health concern with a growing incidence particularly in younger women. Women with early-onset endometrioid EC (EEEC) who wish to maintain fertility are a worldwide concern. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 EECs encompassing 81 EEEC who were 40 or younger. In contrast to late-onset EEC, integrated analysis unexpectedly revealed an exposome-related mutational signature to be associated with EEEC leading to EEEC-specific CTNNB1 and SIGLEC10 hotspot mutations and downstream protein pathway disturbance. Interestingly, in EEECs SIGLEC10Q144K mutation resulted in aberrant Siglec-10 protein expression and promoted progestin resistance by interacting with ERα. Collectively, our study provides a unique high-quality proteogenomic resource of EEECs while enabling insights into interactions between exposome and genomic susceptibilities for primary prevention and early detection of EEECs. Furthermore, we identified biomarkers for progestin response in EEEC fertility-sparing treatment.