Functional Study of MST3, a Human STE20-like Protein Kinase

• Main Authors: Chiung-Yueh, Hsu, 許瓊月
• Other Authors: Dr.Chiun-Jye Yuan
• Format: Others
• Language: en_US
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/40865141262259057841

碩士 === 國立交通大學 === 生物科技研究所 === 88 === MST3, a 52KDa protein, is one of mammalian STE20-like serine/threonine protein kinases with unknown physiological functions. It contains a kinase domain at its N-terminus, while a regulatory domain at its C-terminus. Previous studies have shown that MST3 is a cytoplasmic protein and ubiquitously expressed in many species, including human, mouse, and monkey. Endogenous MST3 was shown to be specifically cleaved by caspase3, caspase7, and 8 during staurosporine or tumor necrosis factor α (TNF-α) - induced apoptosis. Caspase-mediated cleavage of MST3 removes regulatory domain and correlates with a decreased viability of cells expressed with wild-type MST3 and truncated MST3. Overexpression of either wild-type MST3 or a truncated mutant induces a characteristic related to apoptosis. Upon alignment, MST3 contains a potential nuclear localization signal (NLS) sequence located prior to the caspase cleavage site (D313) of MST3. In this study, we demonstrated that amino acids sequence, 278KKTSYLTELIDRYKRWK294, of MST3 play an important role in the nuclear localization of the protein. Wild type of full length MST3 was present predominantly in the cytoplasm, but the truncated form of MST3 was mainly localized in the nucleus. In conclusion, our findings suggest that MST3 could be activated by caspase through cleavage site at D313. Subsequently, the NLS domain of MST3 is exposed and facilitates the nuclear translocation of the protein. The significance of the nuclear translocation of truncated MST3, however, is not clear so far.