Smas C M, Sul H S
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115.
Cell. 1993 May 21;73(4):725-34. doi: 10.1016/0092-8674(93)90252-l.
With the aim of identifying novel regulators of adipocyte differentiation, we have cloned and characterized preadipocyte factor 1 (pref-1), a novel member of the epidermal growth factor (EGF)-like family of proteins. Pref-1 is synthesized as a transmembrane protein with six tandem EGF-like repeats. In preadipocytes, multiple discrete forms of pref-1 protein of 45-60 kd are present, owing in part to N-linked glycosylation. While pref-1 mRNA is abundant in preadipocytes, its expression is completely abolished during differentiation of 3T3-L1 preadipocytes to adipocytes. Moreover, constitutive expression of pref-1 in preadipocytes, which in effect blocks its down-regulation, drastically inhibits adipose differentiation. This indicates that pref-1 functions as a negative regulator of adipocyte differentiation, possibly in a manner analogous to EGF-like proteins that govern cell fate decisions in invertebrates.
为了鉴定脂肪细胞分化的新型调节因子，我们克隆并表征了前脂肪细胞因子1（Pref-1），它是表皮生长因子（EGF）样蛋白家族的一个新成员。Pref-1作为一种具有六个串联EGF样重复序列的跨膜蛋白合成。在前脂肪细胞中，存在多种45-60kd的离散形式的Pref-1蛋白，部分原因是N-糖基化。虽然Pref-1 mRNA在前脂肪细胞中丰富，但其表达在3T3-L1前脂肪细胞向脂肪细胞分化过程中完全消失。此外，Pref-1在前脂肪细胞中的组成型表达实际上阻止了其下调，从而极大地抑制了脂肪分化。这表明Pref-1作为脂肪细胞分化的负调节因子发挥作用，其方式可能类似于在无脊椎动物中决定细胞命运的EGF样蛋白。
