A cell adhesion protein has a second job in stimulating mRNA translation, report Wolf et al.
Plakophilin 1 (PKP1) is an essential component of desmosomes and a member of the armadillo adhesion protein family. Other armadillo proteins, like β-catenin and p120ctn, have additional functions outside of holding cells together: β-catenin is a transcription factor as well as a constituent of adherens junctions, for example. Wolf et al. performed a yeast two-hybrid screen using PKP1 as bait, to see if the desmosomal protein was also capable of moonlighting.
The researchers found that PKP1 binds an ATPase called eIF4A1, a subunit of a cytoplasmic translation initiation complex that recruits ribosomes to the 5′ end of mRNAs. PKP1 overexpression promoted eIF4A1's association with its fellow initiating factors and boosted the translation of mRNAs that depend on this complex. In vitro, PKP1 stimulated eIF4A1's enzymatic activity, which is used to unwind mRNAs and make them accessible to ribosomes. PKP1 isn't essential for translation, but its depletion resulted in small, slowly proliferating cells.
PKP1's ability to stimulate translation may explain why the protein is overexpressed in a number of tumors, says senior author Mechthild Hatzfeld. But cell context is important because PKP1 downregulation can also promote tumorigenesis by reducing cell adhesion. The researchers now want to investigate this dual effect, and determine how the different cellular pools of PKP1 are regulated.