Background: It is unclear how mutations in the coiled-coil tail of ␤-cardiac myosin cause heart disease. Results: Effects of disease-causing mutations in the myosin tail were studied in vivo and in vitro. Conclusion: Mutations that reduce helical content in vitro reduce sarcomere incorporation of myosin in vivo. Significance: A change in myosin tail structure can lead to heart disease.

We have investigated whether the phenotype of myogenic clones derived from satellite cells of different muscles from the transgenic immortomouse depended on muscle type origin. Clones derived from neonatal, or 6-to 12-week-old fast and slow muscles, were analyzed for myosin and enolase isoforms as phenotypic markers. All clones derived from slow-oxidative muscles differentiated into myotubes with a preferentially slow contractile phenotype, whereas some clones derived from rapid-glycolytic or neonatal muscles expressed both fast and slow myosin isoforms. Thus, muscle origin appears to bias myosin isoform expression in myotubes. The neonatal clone (WTt) was cultivated in various medium and substrate conditions, allowing us to determine optimized conditions for their differentiation. Matrigel allowed expressions of adult myosin isoforms, and an isozymic switch from embryonic ␣-toward muscle-specific ␤-enolase, never previously observed in vitro. These cells will be a useful model for in vitro studies of muscle fiber maturation and plasticity.

Class I phosphoinositide 3-kinase (PI3K) enzymes have attracted considerable attention as drug targets in cancer therapy over the last 20 years. The signaling pathway triggered by class I PI3Ks is dysregulated in a range of tumor types, impacting cell proliferation, survival and apoptosis. Frequent oncogenic mutations of PIK3CA have previously been discovered. In contrast, reports of PIK3CB mutations have been limited; however, in most cases, those that have been identified have been shown to be activating and oncogenic. The functional characterization of a PIK3CB catalytic domain mutant, p110βE1051K, first discovered by others in castrate-resistant prostate cancer (mCRPC), is outlined in this report; our data suggest that p110βE1051K is a gain-of-function mutation, driving PI3K signaling, tumorigenic cell growth and migration. Tumor cells expressing p110βE1051K are sensitive to p110β inhibition; its characterization as an oncogenic driver adds to the rationale for targeting p110β and indicates a continuing need to further develop specific PI3K inhibitors for clinical development in cancer therapy.

We conclude that TF can promote immune evasion in tumour cells expressing this protein leading to increased survival and therefore metastatic rate in such cells.

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