Sweet DREAMs for Hippo

Abstract

The Hippo pathway coordinates organ size and cell proliferation. The retinoblastoma family of proteins regulates progression through the G0/G1 phase of the cell cycle. Disruption of either pathway contributes to cancer formation. Three recent studies in Genes & Development reveal how cellular proliferation is coordinated between these pathways. Here we discuss the implications of these studies and the new questions that they raise.

Figure 1.

Conservation of the RB and Hippo signaling pathways in humans and fruit flies. (A) Illustration of the RB pathway from cyclin-dependent kinases to RB family proteins and E2Fs. The names of family members from Drosophila melanogaster and Homo sapiens are indicated. Note that RB family proteins recruit corepressor complexes to E2F promoters using their pocket domain. In the case of p130 (humans) and Rbf2 (fruit fly), the corepressor includes the MuvB core components that assemble into the DREAM and dREAM complexes, respectively. (B) Components of the Hippo pathway are similarly diagrammed, with the names of fruit fly and human counterparts included.

Figure 2.

Mechanisms of coordination between RB and Hippo pathways in cell cycle control. The convergence of Hippo signaling on E2F transcription that was described in recent studies is summarized. (A) A diagram of how Rbf regulates dE2F and Yki/Sd cooperation at E2F target genes in growth-arrested cells. (B) The signaling cascade from LATS to DYRK and p130–DREAM is illustrated to explain how DREAM is assembled to silence E2F target gene expression in growth-arrested cells.