The promiscuous ribosomal P-stalk: a new functional portrait

The canonical role of the ribosome is to translate the genetic code into functional proteins. Recent discoveries, however, redefine the eukaryotic ribosome, as a regulatory hub, that senses cellular cues and transmits signals to downstream pathways. The P-stalk, an integral component of the ribosomal GTPase-associated center, once viewed as translational supporter, is now emerging as a key regulatory ribosomal module. It has recently been recognized as an activator of the integrated stress response, reshaping the Gcn1/Gcn20→Gcn2 axis into the new Gcn1/Gcn20/P-stalk→Gcn2 order. The P-stalk's structural plasticity allows also the ribosome to rewire gene expression in response to cellular demands, including cytokine response. In this review, an updated functional portrait of the P-stalk is presented, encompassing both ribosome-dependent and -independent activities.