PREF-1, A PROTEIN CONTAINING EGF-LIKE REPEATS, INHIBITS ADIPOCYTE DIFFERENTIATION

With the aim of identifying novel regulators of adipocyte differentiat ion, we have cloned and characterized preadipocyte factor 1 (pref-1), a novel member of the epidermal growth factor (EGF)-like family of pro teins. Pref-1 is synthesized as a transmembrane protein with six tande m EGF-like repeats. In preadipocytes, multiple discrete forms of pref- 1 protein of 45-60 kd are present, owing in part to N-linked glycosyla tion. While pref-1 mRNA is abundant in preadipocytes, its expression i s completely abolished during differentiation of 3T3-L1 preadipocytes to adipocytes. Moreover, constitutive expression of pref-1 in preadipo cytes, which in effect blocks its down-regulation, drastically inhibit s adipose differentiation. This indicates that pref-1 functions asa ne gative regulator of adipocyte differentiation, possibly in a manner an alogous to EGF-like proteins that govern cell fate decisions in invert ebrates.