MITF links maturation and quiescence

The coordination of cell differentiation with exit from the cell division cycle may help to limit organ size and prevent tumor formation. But the mechanism that links these two processes is unknown for most cell types. On page 35, Loercher et al. show that, in melanocytes, the link is the MITF transcription factor.

MITF was already known for its differentiation-inducing activity. Now it is also shown to slow cell growth by activating transcription of a cell cycle inhibitor gene (in addition to pigment and melanocyte survival genes). This mitotic inhibitor, p16^Ink4a, arrests cells in G1 by blocking phosphorylation of Rb. Hypophosphorylated Rb binds to E2F and thus prevents it from activating cell cycle progression genes.

The cell cycle arrest is needed for differentiation, as precursor...