Enterophilins, a new family of leucine zipper proteins bearing a B30.2 domain and associated with enterocyte differentiation

Enterocyte terminal differentiation occurs at the crypt-villus junction thr ough the transcriptional activation of cell-specific genes, many of which c ode for proteins of the brush border membrane such as intestinal alkaline p hosphatase, sucrase-isomaltase, or the microvillar structural protein villi n, Several studies have shown that this sharp increase in specific mRNA lev els is intimately associated with arrest of cell proliferation. We isolated several clones from a guinea pig intestine cDNA library, They encode new p roteins characterized by an original structure associating a carboxyl-termi nal B30.2/RFP-like domain and a long leucine zipper at the amino terminus. The first member of this novel gene family codes for a 65-kDa protein terme d enterophilin-1, which is specifically expressed in enterocytes before the ir final differentiation. Enterophilin-1 is the most abundant in the small intestine but is still present in significant amounts in colonic enterocyte s. In Caco-2 cells, a similar 65-kDa protein was recognized by a specific a nti-enterophilin-1 antibody, and its expression was positively correlated w ith cell differentiation status. In addition, transfection of HT-29 cells w ith enterophilin-1 full-length cDNA slightly inhibited cell growth and prom oted an increase in alkaline phosphatase activity. Taken together, these da ta identify enterophilins as a new family of proteins associated with enter ocyte differentiation.