Transcriptional control through subcellular localization

Although this might seem more than sufficient to control the subcellular distribution of PBC proteins, an additional mechanism comes into play at the level of cytoplasmic retention (Fig. 4). The action of a cytoplasmic retention factor was inferred from the observation that a fraction of PBC protein is resistant to LMB-induced nuclear accumulation (Abu-Shaar et al., 1999 Saleh et al., 

Although their function is no doubt affected by the nuclear availability of EXD, HOX proteins in turn control the levels of hth and exd expression. Thus, exd transcripts are reduced in the abdomen of the fly embryo through the action of BX-C Hox genes (Rauskolb et ah, 1993), and Scr, Antp, Ubx and abd-A all repress hth transcription (Casares and Mann, 1998 Kurant et ah, 1998 Yao et ah, 1999). These effects on hth expression may account for the ability of BX-C Hox genes to inhibit the nuclear localization of EXD (Azpiazu and Morata, 1998). The multiplicity of controls at the levels of transcription, subcellular localization, and protein turnover suggests that the functions of EXD and HTH, both with and without HOX partners, must be carefully titrated to direct developmental programs appropriately. 

This may be necessary to set the correct ratios of various complexes—PBC-PBC, PBC-MEIS/PREP, PBC HOX-MEIS/PREP—with potentially opposing activities. This presumed importance of the levels of EXD and HTH stands in contrast to data suggesting that HOX proteins exert similar effects over a range of concentrations (Castelli-Gair and Akam, 1995). 

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