Identifying serum-inducible sequence elements on the mouse ZFP36 promoter

Immediate-early genes are characterized by immediate transcriptional activation upon appropriate stimulation, including treatment of cells with mitogen-containing serum, without any need for intervening protein synthesis (Johansen, 1995). As they are among the !rst genes to be activated in many signaling pathways, immediate-early genes provide a gateway to study the cellular response. Zinc !nger protein 36 (ZFP36) is an immediate-early gene product that regulates the expression of some genes by destabilizing their mRNA. "e protein binds to AU-rich sequences on mRNA and catalyzes removal of the polyadenylated tail, reducing the half-life of the RNA (Blackshear, 2002). "e zinc !nger motif is common in DNA and RNA binding proteins, though ZFP36 is unusual in that it has a Cys3-His zinc-coordinating domain, as opposed to the more common Cys2-His2 domain (Tchen, 2004). "is slight di#erence in peptides might subtly impact the nucleotide binding dynamics of ZFP36. Notable genes regulated in part by ZFP36 include tumor necrosis factor(TNF), epidermal growth factor (EGF) and c-fos, a transcription factor that promotes proliferation (Amit, 2007) Mice de!cient in ZFP36 develop an excess of TNF, and the overabundance of this cytokine results in autoimmune complications such as arthritis (Lai, 1998). As EGF and c-fos are both implicated in proliferation, ZFP36 is also thought to act as a tumor-suppressor (Amit, 2007)