Muscle differentiation, like many aspects of development, is controlled by interplay between different signalling molecules and cell fate determinants. The MyoD and MEF2 transcription factors play key roles in the process, as does signalling by insulin-like growth factors (IGFs), which activate the kinases PI3K and Akt (also known as PKB). On , Zhenguo Wu and coworkers establish a link between these myogenic regulators and along the way uncover a role for prohibitin 2 (PHB2) - a highly conserved protein whose function has so far remained elusive. Picking up PHB2 in two-hybrid screens for Akt-binding partners, the authors demonstrate that it is a transcriptional repressor that can inhibit MyoD- and MEF2-dependent transcription in C2C12 myoblasts and block muscle differentiation. They also show that it interacts with endogenous MyoD and MEF2 and inhibits transcription by recruiting the histone deacetylase HDAC1. Wu and coworkers go on to reveal that Akt promotes muscle differentiation by disrupting binding of PHB2 to MyoD, which allows the transcription factor to execute its function. Their findings therefore highlight a lesser-known aspect of Akt function: its kinase-independent effects.
