The IER3 gene spans 1351 bp genomic DNA and consists of 2 coding exons. The coding sequence of IER3 is 498 nucleotides long.

IER3 as well as its rodent homologues PRG1 and gly96 consists of 156, 160 and 153 amino acids, respectively, and, to current knowledge, share no significant sequence similarities with any other known protein. IER3 shuttles between the cytoplasm and the nucleus (Kruse et al., 2005) where it accumulates in promyelocytic nuclear dots, unique structures that are involved in stress response. IER3 is also localized in the mitochondrial membrane where it interferes with the ATP producing system (Shen et al., 2009).

Epithelial cells, keratinocytes, hepatocytes, monocytes, lymphocytes.

Nucleus, mitochondrial membrane, cytoplasm.

Immediate early gene X-1 (IEX-1), also known as IER3/DIF2, is a growth and stress associated early response gene (Kondratyev et al., 1996; Schäfer et al., 1996) involved in a great variety of cellular functions (Wu, 2003). The expression of IER3 is under control of many stimuli and cellular conditions including growth factors, cytokines, viral infection, UV- and gamma-irradiation or biomechanical strain. Recent data demonstrated that IER3 modulates cell cycle progression and proliferation, as well as programmed cell death in a cell type- and stimulus-dependent fashion (Wu, 2003).
A line of functional studies revealed that IER3 exerts a dual role in cellular growth control and apoptosis. For example, in epithelial cells, hepatocytes and keratinocytes IER3 enhances apoptosis (Schilling et al., 2001; Arlt et al., 2007; Arlt et al., 2008; Sebens Muerkoster et al., 2008) whereas in hematological precursor cells and in immune cells IER3 rather favours cellular survival and differentiation (Wu, 2003; Mittal et al., 2006; Rocher et al., 2007; Rocher et al., 2007).
Recent studies revealed that IER3 expression is inversely related to the formation of malignant tumors such as colon cancer (Nambiar et al., 2004; Sebens Muerkoster et al., 2008), pancreatic cancer (Sasada et al., 2008) and endocrine tumors (Dilley et al., 2005), thus pointing to a tumor suppressive potential of IER3. Obviously, the cellular actions of IER3 are complex depending on cell type and context related conditions but one mechanism by which IER3 could affect cellular viability is the negative interference with NF-kappaB activation. To some extent this action of IER3 relies on the dampening of IkappaB degradation thereby leading to a reduced nuclear localization of NF-kappaB (Arlt et al., 2001; Arlt et al., 2003; Arlt et al., 2007).
Moreover, a recent study demonstrated that IER3 is also capable to directly bind to p65/RelA leading to the inhibition of p65-dependent gene transcription (Arlt et al., 2008). Thus, IER3 is supposed to be part of a NF-kappaB dependent counterregulatory mechanism that might be particularly relevant in the control of immune responses.
Consequently, an impaired NF-kappaB control may promote severe inflammatory processes and carcinogenesis.

None.

IEX-1L : Non spliced variant encoding the apoptosis inhibitor IEX-1L (Wu et al., 1998). This gene product does not derive from regular pre-mRNA splicing nor from a second gene but represents a triple mutated form of IEX-1/IER3 (Schäfer et al., 1999). This mutant variant has been artificially produced and acts as a dominant negative suppressor of wild type IEX-1/IER3 (Schäfer et al., 1999).