Regulation of hyaluronan synthases: negative effects on the hyaluronan synthetic activity of the mutated HAS protein that has no enzymatic activity

Abstract

Hyaluronan (HA), one of major components of mammalian extracellular matrices, is heavily involved in the regulation of a variety of cellular behaviors, such as cell proliferation and cell migration. Three isoforms of hyaluronan synthase (HAS1, 2, and 3) derived from the different genes in mammals have different enzymatic properties, and are responsible for the HA synthesis. In order to investigate the possible involvement of HA in abnormal cell properties, such as cancer metastasis and mechanisms, it may be worth determining methods for regulating each hyaluronan synthase activity, or the total activity. We examined the effect of the mutated HAS protein which did not show HA synthetic activity. Co-transfection with the mutated HAS gene and each wild-type HAS gene resulted in a reduction of the activity of all isoforms. These results suggest that each HAS protein is able to assemble or to interact with itself or other isoforms in order to regulate its own activity. This method could be applicable for regulating HAS activity in vivo.