THE NEUROENDOCRINE PROTEIN 7B2 CONTAINS UNUSUALLY POTENT TRANSCRIPTIONAL ACTIVATING SEQUENCES

The expression of the 7B2 protein, secreted from a variety of neural a nd endocrine tissues, increases dramatically in specific neuroendocrin e tumors. We have recently shown that human 7B2 can act as a molecular chaperone in the deaggregation of proteins in vitro. In order to iden tify polypeptides which might bind 7B2 in viva, the yeast two-hybrid s ystem was employed. Surprisingly, mere covalent linkage of 7B2 to the DNA-binding domains of two yeast transcription activators, Ace1 and Ga l4, activates transcription from the ACE1 and GAL4 operon. 7B2's abili ty to activate nuclear transcription surpasses that of Ace1 and compar es favourably with the strong activation domain of the tumor suppresso r protein, p53. Our results suggest that 7B2 must possess an activatin g sequence, a domain which defines all transcriptional activator prote ins. Like the acidic activation domains of some transpirational activa tors, 7B2 also binds the yeast TATA-box binding protein, an essential polypeptide in the basic transcription machinery. Deletion analysis of the gene encoding 7B2 reveals two independent transcriptional activat ing sequences in the 185 amino acid protein. It is therefore conceivab le that 7B2 not only has a functional role in the secretory pathway bu t also in the nucleus. Moreover, these findings raise an intriguing qu estion regarding the activation domains of 7B2 and their possible link to 7B2's oncogenic potential. (C) 1995 Academic Press, Inc.