The Threonine Protease Activity of Testes-Specific Protease 50 (TSP50) Is Essential for Its Function in Cell Proliferation

Background: Testes-specific protease 50 (TSP50), a newly discovered threonine enzyme, has similar amino acid sequences and enzymatic structures to those of many serine proteases. It may be an oncogene. TSP50 is up-regulated in breast cancer epithelial cells, and ectopic expression of TSP50 in TSP50-deficient Chinese hamster ovary (CHO) cells has been found to promote cell proliferation. However, the mechanisms by which TSP50 exerts its growth-promoting effects are not yet fully understood. Methodology/Principal Findings: To delineate whether the threonine protease activity of TSP50 is essential to its function in cell proliferation, we constructed and characterized a mutant TSP50, called TSP50 T310A, which was identified as a protease-dead mutant of TSP50. By a series of proliferation analyses, colony formation assays and apoptosis analyses, we showed that T310A mutation significantly depresses TSP50-induced cell proliferation in vitro. Next, the CHO stable cell line expressing either wild-type or T310A mutant TSP50 was injected subcutaneously into nude mice. We found that the T310A mutation could abolish the tumorigenicity of TSP50 in vivo. A mechanism investigation revealed that the T310A mutation prevented interaction between TSP50 and the NF-kBIkBa complex, which is necessary for TSP50 to perform its function in cell proliferation. Conclusion: Our data highlight the importance of threonine 310, the most critical protease catalytic site in TSP50, to TSP50induce

Do Mutual Funds Have Decreasing Returns to Scale? Evidence from Fund Mergers

Using fund mergers as shocks to fund size, I analyze return-to-scale properties of mutual funds. The results show that acquiring funds experience performance deterioration after abnormal size increases due to mergers. Funds that have a larger shock in size at the time of mergers are more likely to experience worse declines in performance after the events. In the post-merger period, investors redeem their shares from the poorly performing acquiring funds, and both the declining performance and persistent capital outflows lead to decreases in size. As fund size decreases, performance tends to recover. These findings provide evidence that is consistent with mutual funds having decreasing returns to scale and more broadly with theoretical models of delegated portfolio, such as Berk and Green (2004)

Do Mutual Funds Have Decreasing Returns to Scale? Evidence from Fund Mergers

Using fund mergers as shocks to fund size, I analyze return-to-scale properties of mutual funds. The results show that acquiring funds experience performance deterioration after abnormal size increases due to mergers. Funds that have a larger shock in size at the time of mergers are more likely to experience worse declines in performance after the events. In the post-merger period, investors redeem their shares from the poorly performing acquiring funds, and both the declining performance and persistent capital outflows lead to decreases in size. As fund size decreases, performance tends to recover. These findings provide evidence that is consistent with mutual funds having decreasing returns to scale and more broadly with theoretical models of delegated portfolio, such as Berk and Green (2004)