Zhichuan (Frank) Li

We study how corporate governance moderates the relationship between corporate social responsibility (CSR), corporate social irresponsibility (CSI), and firm risk. We find that CSR reduces risk for firms with strong governance. In contrast, CSI increases firm risk more significantly for firms with stronger governance, suggesting that backlash is more severe when well‐governed firms engage in irresponsible behavior. Overall, our evidence indicates that the negative impact of CSI for well‐governed firms outweighs the risk‐reducing benefits of CSR. These findings provide strong support for information intensity arguments.

This article studies the relationship between CEOs' social media activity and their insider trading behavior. Drawing on psychological evidence linking online activity to risk‐taking, we find that active CEOs on social media exhibit higher risk preferences and engage more in insider trading—particularly in terms of incidence, intensity, and profitability. The effects are primarily driven by insider buys (rather than sells), which are more likely to involve material non‐public information, and such opportunistic trades may increase firm reputational risk. Further analysis reveals that certain corporate governance mechanisms, such as blackout policies and compensation structures, help mitigate the negative impact.

This article empirically examines the role of a firm's second‐in‐command in monitoring the chief executive officer (CEO) from the bottom up to mitigate agency problems. Although CEOs have long been the focus, little research has addressed No. 2 executive. This study provides a comprehensive understanding of these top executives and their roles in bottom‐up monitoring. The results suggest that (1) bottom‐up monitoring by No. 2 executives enhances firm value, (2) the effect is stronger in firms with weak corporate governance or poor CEO incentive alignment, (3) the effect is weaker when No. 2 is promoted internally or lacks experience, and (4) such monitoring becomes more critical in the post‐Sarbanes–Oxley (SOX) regulatory environment. Further analysis reveals that bottom‐up monitoring creates firm value by fostering a more transparent information environment, increasing CEO turnover‐performance sensitivity, and reducing the CEO's ability to pursue the “quiet life,” but has no effect on “empire building.”

P53 is regulated at multiple levels. We report here that p53, in multiple lines of human cancer cells, is down-regulated by cardiac glycoside drugs digoxin and ouabain, potent inhibitors of Na+/K+-ATPase. These drugs reduced the basal levels of p53 protein at nanomolar concentrations in a dose-, time-, and cancer cell line–dependent manner, but independent of p53 status of wild-type or mutant. The drugs also reduced the levels of p53 induced by its activators as well as p53 transfected into human cancer cells, regardless of its status. Interestingly, the drugs had no effect on endogenous p53 in two immortalized human cell lines. Mechanistically, p53 reduction occurred not at the mRNA levels but at the protein levels, as a result of reduced protein synthesis rather than enhanced degradation. The cellular sensitivity to drug-induced p53 reduction was not associated with the levels of αsubunits of Na+/K+-ATPase in different cell lines. Although lowering extracellular K+ did not reduce p53 as did ouabain and digoxin, it did potentiate both digoxin- and ouabain-induced p53 reduction in sensitive lines. Finally, p53 reduction seems to be triggered by activation of Src/mitogen-activated protein kinase (MAPK) signaling pathways upon drug binding to the Na+/K+-ATPase and can be completely blocked by the inhibitors of Src or MAP/ERK kinase. This is the first report that cardiac glycoside drugs, by initiating the Src/MAPK signaling pathways, reduce the p53 levels via inhibition of p53 protein synthesis. The drugs may be useful in the treatment of human cancers with a gain-of-function p53 mutation. [Cancer Res 2009;69(16):6556–64]

P53 is regulated at multiple levels. We report here that p53, in multiple lines of human cancer cells, is down-regulated by cardiac glycoside drugs digoxin and ouabain, potent inhibitors of Na+/K+-ATPase. These drugs reduced the basal levels of p53 protein at nanomolar concentrations in a dose-, time-, and cancer cell line–dependent manner, but independent of p53 status of wild-type or mutant. The drugs also reduced the levels of p53 induced by its activators as well as p53 transfected into human cancer cells, regardless of its status. Interestingly, the drugs had no effect on endogenous p53 in two immortalized human cell lines. Mechanistically, p53 reduction occurred not at the mRNA levels but at the protein levels, as a result of reduced protein synthesis rather than enhanced degradation. The cellular sensitivity to drug-induced p53 reduction was not associated with the levels of αsubunits of Na+/K+-ATPase in different cell lines. Although lowering extracellular K+ did not reduce p53 as did ouabain and digoxin, it did potentiate both digoxin- and ouabain-induced p53 reduction in sensitive lines. Finally, p53 reduction seems to be triggered by activation of Src/mitogen-activated protein kinase (MAPK) signaling pathways upon drug binding to the Na+/K+-ATPase and can be completely blocked by the inhibitors of Src or MAP/ERK kinase. This is the first report that cardiac glycoside drugs, by initiating the Src/MAPK signaling pathways, reduce the p53 levels via inhibition of p53 protein synthesis. The drugs may be useful in the treatment of human cancers with a gain-of-function p53 mutation. [Cancer Res 2009;69(16):6556–64]

Supplementary Figure Legends 1-4 from Cardiac Glycosides Inhibit p53 Synthesis by a Mechanism Relieved by Src or MAPK Inhibition

Supplementary Figure Legends 1-4 from Cardiac Glycosides Inhibit p53 Synthesis by a Mechanism Relieved by Src or MAPK Inhibition

Supplementary Figures 1-4 from Cardiac Glycosides Inhibit p53 Synthesis by a Mechanism Relieved by Src or MAPK Inhibition

Supplementary Figures 1-4 from Cardiac Glycosides Inhibit p53 Synthesis by a Mechanism Relieved by Src or MAPK Inhibition