MYH9

Pancreatic ductal adenocarcinoma (PDAC) is the most malignant tumor. Zinc finger and SCAN domain-containing protein 23 (ZSCAN23) is a new member of the SCAN domain family. The expression regulation and biological function remain to be elucidated. In this study, we explored the epigenetic regulation and the function of ZSCAN23 in PDAC. ZSCAN23 was methylated in 60.21% (171/284) of PDAC and its expression was regulated by promoter region methylation. The expression of ZSCAN23 inhibited cell proliferation, colony formation, migration, invasion, and induced apoptosis and G1/S phase arrest. ZSCAN23 suppressed Panc10.05 cell xenograft growth in mice. Mechanistically, ZSCAN23 inhibited Wnt signaling by interacting with myosin heavy chain 9 (MYH9) in pancreatic cancer cells. ZSCAN23 is frequently methylated in PDAC and may serve as a detective marker. ZSCAN23 suppresses PDAC cell growth both in vitro and in vivo.

While protein homeostasis is a hallmark of gene regulation, unraveling the hidden regulatory mechanisms that maintain homeostasis is difficult using traditional methods. To confront this problem, we CRISPR engineered a human cell line with multiple tags in the endogenous MYH9 gene, which encodes the essential and ubiquitous myosin-2A cytoskeletal motor. Using these cells, we imaged MYH9 transcription, translation, and mature mRNA and protein in distinct colors, enabling a full dissection of the central dogma. Our data show that MYH9 transcription is upregulated in an SRF-dependent manner in response to cytoskeletal cues and that MYH9 translation can either buffer or match the transcriptional response depending on context. Upon knockdown of actin-depolymerizing proteins like cofilin, translation efficiency drops by a factor of two to buffer strong transcriptional upregulation, likely to help prevent excessive myosin activity. In contrast, following serum stimulation, translation matches the transcriptional response to readily reestablish steady state. Our results identify contextual translational buffering as an important regulatory mechanism driving stable MYH9 expression. They also demonstrate the power and broad applicability of our cell line, which can now be used to accurately quantify central dogma dynamics in response to diverse forms of cellular perturbations.

Understanding the basic solubilization of fish myofibrillar proteins (MPs) in common monovalent chloride solutions is crucial for muscle food processing. In this study, the differential proteomic profiles of MPs during extraction and solubilization in NaCl and KCl solutions were investigated by using advanced four-dimensional data-independent acquisition (4D DIA) quantitative proteomics for the first time. Compared to routine biochemical analysis, this could provide insights into the solubilization of muscle proteins. We ensure the consistency of the effective ionic strength of NaCl and KCl buffers by adjusting the conductivity. The results showed that NaCl extractor mainly facilitated the solubilization of cytoskeletal proteins, biochemical enzymes, and stromal proteins compared to KCl, such as tubulin, myosin-9, collagen, plectin, protein phosphatase, and cathepsin D. However, no significant difference was observed in the extraction of major sarcomeric proteins, including myosin, actin, troponin C, myosin-binding protein C, M-Protein, α-actinin-3, and tropomyosin.