IRES-like elements are present in other viral systems and were recently discovered in eukaryotic cells which give certain mRNA molecules cap-independent translation ability in response to viral infection or stress conditions, as was shown for immunoglobulin heavy chain binding protein (Bip) and the cap-binding protein eIF4G (Macejak and Sarnow, 1991; Gan and Rhoads, 1996) (Table 1) . Cap-independent translation can also enforce an alternative translation start site, resulting in translation of different proteins from the same mRNA, such as that mediated by the human fibroblast growth factor 2 (FGF2) (Vagner et al., 1995) . Recently, IRES elements were also identified in the translation regulation of developmentally regulated genes such as the homeotic gene Antennapedia or Ultrabithorax of Drosophila (Oh et al., 1992; Ye et al., 1997) , the genes for human insulinlike growth factor (IGF-II) (Teerink et al., 1995) , and the platelet-derived growth factor B (developmental IRES or D-IRES; Bernstein et al., 1997) . The potential for cap-independent translation-initiation has also been found in yeast and Xenopus oocytes (Iizuka et al., 1994; Kneiper and Rhoads, 1997) . Furthermore, the finding of an internal ribosomal entry site in the 5 untranslated region of c-myc suggests that IRES- Figure 1 . Strategies for simultaneous and in some cases regulated expression of more than one gene in mammalian cells. Key genetic elements for expression in mammalian cells such as the promoter (P), internal ribosomal entry sites of polioviralorigin (IRES) or derived from the encephalomyocarditis virus (CITE), the splice donor (SD) and acceptor (SA) and the polyadenylation site (PA) as well as for regulated gene expression including the tetracycline-responsive transactivator (tTA) and the tet-responsive promoter (P hCMV * −1 ) are indicated. In some cases translation is shown below the genetic configuration (mRNA, ribosome, proteins). Iizuka et al., 1994 mediated translational control may be vital for higher organisms as aberrant translational regulation of cmyc is likely to play a role in tumorigenesis (Stoneley et al., 1998) .