“This is a really new concept—that chromatin-associated proteins are shuttling,” says Baur. The shuttling Eed protein, a polycomb group (PcG) heterochromatin factor, is captured at the plasma membrane by either membrane-associated Nef or activated integrins.
Eed first came to the attention of the German group as a Nef-binding protein. Injection of Nef into cells led to translocation of Eed out of nuclei to the cytoplasm. This reduces or eliminates the association of Eed with the integrated HIV DNA and increases HIV transcription. During an infection, these effects may be mediated by the small amount of Nef that the virus brings in with it.
The interaction between Eed and integrins has been noted before, but Witte et al. are the first to demonstrate that Eed shuttles out of the nucleus and binds to the plasma membrane after integrin activation, thus increasing HIV transcription.
The capture of Eed at signaling complexes may, Baur suggests, ensure that the nucleus is derepressed even before it receives activating signals from the plasma membrane. Other signaling complexes may use the same dual strategy. ▪