Negative regulation of STAT92E by an N-terminally truncated STAT protein derived from an alternative promoter site

Abstract

Previously unrecognized mRNAs originating from a dual promoter at the stat92E locus are described. One of these encodes a truncated protein, ΔNSTAT92E, that lacks the N-terminal 133 amino acids. Antibodies detect both the full-length and truncated molecules early in embryogenesis (1-5 h), and mRNA detection by specific RT-PCR reactions accords with the protein distribution. Given that the N termini of mammalian STATs are known to have positive functions in transcriptional activation, we explored the role of ΔNSTAT92E early in embryogenesis. By increasing the ΔNSTAT92E-to-STAT92E ratio in overexpression and RNAi experiments, we observe phenotypes compatible with suppression of wild-type STAT92E activity. We therefore conclude that the short form of STAT92E is a naturally occurring dominant-negative product that can be added to the growing list of negative regulators of STAT activity.