Inhibition of protein phosphatase 2A (PP2A) activity has been identified as a prerequisite for the transformation of human cells. However, the molecular mechanisms by which PP2A activity is inhibited in human cancers are currently unclear. In this study, we describe a cellular inhibitor of PP2A with oncogenic activity. The protein, designated Cancerous Inhibitor of PP2A (CIP2A), interacts directly with the oncogenic transcription factor c-Myc, inhibits PP2A activity toward c-Myc serine 62 (S62), and thereby prevents c-Myc proteolytic degradation. In addition to its function in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation. The oncogenic activity of CIP2A is demonstrated by transformation of human cells by overexpression of CIP2A. Importantly, CIP2A is overexpressed in two common human malignancies, head and neck squamous cell carcinoma (HNSCC) and colon cancer. Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies.
Acute haemorrhagic pancreatitis was induced in rats by injecting aqueous solution of sodium taurocholate into the common biliopancreatic duct. Lecithin and lysolecithin were separated from pulmonary homogenate by thin layer chromatography and quantified by phosphorus determination. The ratio of lysolecithin to lecithin increased after the sodium taurocholate injection as well as after i.v. administration of porcine pancreatic phospholipase A2. It was concluded that phospholipase A2, released from pancreatic acinar cells into blood, may convert pulmonary lecithin into lysolecithin during acute pancreatitis. Destruction of pulmonary surfactant may contribute to the development of the adult respiratory distress syndrome as seen in patients suffering from severe acute pancreatitis.
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