Instead of packing the dishes and submitting a change of address form, a cell that is about to move replaces its surface proteins, revamps its cytoskeleton, and alters its shape. Lander et al. show that one enzyme serves as a master controller for this process.
A cell's pre-move preparations are referred to as the epithelial–mesenchymal transition (EMT). Embryonic cells undergo EMT before they relocate during develoment, as do tumor cells that are about to metastasize. Researchers are still working out how cells regulate EMT so that the molecular and behavioral changes occur in concert and at the right time. Thus far, they have shown that the transcription factors Slug, Snail, Twist, and Sip1 help activate EMT. In turn, the enzyme Partner of paired (Ppa) adjusts the levels of Slug and Snail, triggering their ubiquitination so that they can be destroyed by the proteasome.
Lander et al. discovered that Ppa also controls cellular quantities of Twist and Sip1 by promoting their ubiquitination. Thus Ppa regulates all four of the EMT-triggering transcription factors, despite their structural differences. Using the same protein to manage Slug, Snail, Twist, and Sip1 may ensure that the transcription factors work in synchrony and that their effects can be shut down simultaneously. The work also suggests that it might be possible to curtail metastasis by targeting Ppa to disrupt EMT.
