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Annexin A2 extracellular translocation and virus interaction: A potential target for antivirus-drug discovery

Aliyu IA, Ling KH, Md Hashim N, Chee HY

Rev Med Virol, 2019 05;29(3):e2038.
PMID: 30746844 DOI: 10.1002/rmv.2038

Annexin A2 is a membrane scaffolding and binding protein, which mediated various cellular events. Its functions are generally affected by cellular localization. In the cytoplasm, they interacted with different phospholipid membranes in Ca2+ -dependent manner and play vital roles including actin binding, remodeling and dynamics, cytoskeletal rearrangement, and lipid-raft microdomain formation. However, upon cell exposure to certain stimuli, annexin A2 translocates to the external leaflets of the plasma membrane where annexin A2 was recently reported to serve as a virus receptor, play an important role in the formation of virus replication complex, or implicated in virus assembly and budding. Here, we review some of annexin A2 roles in virus infections and the potentiality of targeting annexin A2 in the design of novel and promising antivirus agent that may have a broader consequence in virus therapy.

Matched MeSH terms: Annexin A2/metabolism*
Fulltext Proteomic Analysis of Anticancer Effect of Myo-inositol in Human Prostate Cancer (DU-145) Cell Line

Islam MJ, Muntaha S, Masum MM, Nowshin S, Salam S, Haque M, et al.

Asian Pac J Cancer Prev, 2024 Dec 01;25(12):4447-4455.
PMID: 39733438 DOI: 10.31557/APJCP.2024.25.12.4447

OBJECTIVE: This study investigated the potential anticancer properties of Myo-inositol on the DU-145 prostate cancer cell line.
METHODS: The DU-145 cells have been treated to different doses of Myo-inositol in order to ascertain the half-maximal inhibitory concentration (IC50) using the trypan blue exclusion assay. The impact of Myo-inositol on proteomic profiles was evaluated using 2D gel electrophoresis and liquid chromatography-mass spectrometry (LC-MS).
RESULTS: Myo-inositol significantly reduced DU-145 cell viability with an IC50 of 0.06 mg/ml (p<0.05). Proteomic analysis highlighted marked differences in protein expression between treated and untreated cells, particularly in proteins related to cytoskeletal regulation, apoptosis, and stress response. LC-MS further identified significant alterations in protein profiles, with suppression of proteins like Annexin A2 and Cofilin-1-A in controls, and upregulation of proteins such as Rho GTPase-activating protein, Apoptotic protease-activating factor 1 (APAF1), and TNF receptor-associated factor 2 (TRAF2) in treated samples (p<0.001), indicating modulation of key signaling pathways involved in tumor suppression and oncogenesis.
CONCLUSION: Myo-inositol exhibits anticancer properties in prostate cancer cells by impacting cell viability and altering protein expression. While promising as an adjunctive treatment, further studies are needed to understand its mechanisms and potential in combination therapies for managing CRPC.

Matched MeSH terms: Annexin A2/metabolism
Annexin A2 and alpha actinin 4 expression correlates with metastatic potential of primary endometrial cancer

Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Kaur G, Anderson L, et al.

Biochim Biophys Acta Proteins Proteom, 2017 Jul;1865(7):846-857.
PMID: 27784647 DOI: 10.1016/j.bbapap.2016.10.010

The prediction of lymph node metastasis using clinic-pathological data and molecular information from endometrial cancers lacks accuracy and is therefore currently not routinely used in patient management. Consequently, although only a small percentage of patients with endometrial cancers suffer from metastasis, the majority undergo radical surgery including removal of pelvic lymph nodes. Upon analysis of publically available data and published research, we compiled a list of 60 proteins having the potential to display differential abundance between primary endometrial cancers with versus those without lymph node metastasis. Using data dependent acquisition LC-ESI-MS/MS we were able to detect 23 of these proteins in endometrial cancers, and using data independent LC-ESI-MS/MS the differential abundance of five of those proteins was observed. The localization of the differentially expressed proteins, was visualized using peptide MALDI MSI in whole tissue sections as well as tissue microarrays of 43 patients. The proteins identified were further validated by immunohistochemistry. Our data indicate that annexin A2 protein level is upregulated, whereas annexin A1 and α actinin 4 expression are downregulated in tumours with lymph node metastasis compared to those without lymphatic spread. Moreover, our analysis confirmed the potential of these markers, to be included in a statistical model for prediction of lymph node metastasis. The predictive model using highly ranked m/z values identified by MALDI MSI showed significantly higher predictive accuracy than the model using immunohistochemistry data. In summary, using publicly available data and complementary proteomics approaches, we were able to improve the prediction model for lymph node metastasis in EC.

Matched MeSH terms: Annexin A2/metabolism*
Fulltext Annexin II Light Chain p11 Interacts With ENaC to Increase Functional Activity at the Membrane

Cheung TT, Ismail NAS, Moir R, Arora N, McDonald FJ, Condliffe SB

Front Physiol, 2019;10:7.
PMID: 30800070 DOI: 10.3389/fphys.2019.00007

The epithelial Na+ channel (ENaC) provides for Na+ absorption in various types of epithelia including the kidney, lung, and colon where ENaC is localized to the apical membrane to enable Na+ entry into the cell. The degree of Na+ entry via ENaC largely depends on the number of active channels localized to the cell membrane, and is tightly controlled by interactions with ubiquitin ligases, kinases, and G-proteins. While regulation of ENaC endocytosis has been well-studied, relatively little is understood of the proteins that govern ENaC exocytosis. We hypothesized that the annexin II light chain, p11, could participate in the transport of ENaC along the exocytic pathway. Our results demonstrate that all three ENaC channel subunits interacted with p11 in an in vitro binding assay. Furthermore, p11 was able to immunoprecipitate ENaC in epithelial cells. Quantitative mass spectrometry of affinity-purified ENaC-p11 complexes recovered several other trafficking proteins including HSP-90 and annexin A6. We also report that p11 exhibits a robust protein expression in cortical collecting duct epithelial cells. However, the expression of p11 in these cells was not influenced by either short-term or long-term exposure to aldosterone. To determine whether the p11 interaction affected ENaC function, we measured amiloride sensitive Na+ currents in Xenopus oocytes or mammalian epithelia co-expressing ENaC and p11 or a siRNA to p11. Results from these experiments showed that p11 significantly augmented ENaC current, whereas knockdown of p11 decreased current. Further, knockdown of p11 reduced ENaC cell surface population suggesting p11 promotes membrane insertion of ENaC. Overall, our findings reveal a novel protein interaction that controls the number of ENaC channels inserted at the membrane via the exocytic pathway.

Matched MeSH terms: Annexin A2