Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of eukaryotic cell regulation, and MAPK has a close relationship with cardiovascular development and diseases such as cardiomyotrophy. Overexpression of hole in the COS-7 cells inhibits strongly the transcriptional activities of AP-1 and SRE. Hole functions as a inhibitor probably through its ERK D-domian in N-terminal and proline-rich region in C-terminal. The results suggest that hole might be involved in heart development through MAPK signaling pathway.