ING2 as a novel mediator of transforming growth factor-beta-dependent responses in epithelial cells.

Members of the ING (inhibitor of growth) family of chromatin modifying proteins (ING1-ING5) have emerged as critical regulators of gene expression and cellular responses, suggesting that the ING proteins may impinge on specific signal transduction pathways and their mediated effects. Here, we demonstrate a role for the protein ING2 in mediating responses by the transforming growth factor (TGF)-beta-Smad signaling pathway. We show that ING2 promotes TGF-beta-induced transcription. Both gain-of-function and RNA interference-mediated knockdown of endogenous ING2 reveal that ING2 couples TGF-beta signals to the induction of transcription and cell cycle arrest. We also find that the Smad-interacting transcriptional modulator SnoN interacts with ING2 and promotes the assembly of a protein complex containing SnoN, ING2, and Smad2. Knockdown of endogenous SnoN blocks the ability of ING2 to promote TGF-beta-dependent transcription, and conversely expression of SnoN augments ING2 enhancement of the TGF-beta response. Collectively, our data suggest that ING2 collaborates with SnoN to mediate TGF-beta-induced Smad-dependent transcription and cellular responses.