Figure 4

Catalytic-independent functions of MAPKs. (A) Topoisomerase IIa, involved in winding and unwinding of DNA, is activated by ERK by a phosphorylation-independent process. (B) Activated ERK2 interacts with PolyADP-ribose polymerase 1 (PARP-1) and activates it independent of ERK kinase activity and DNA strand breaks. (C) ERK can repress INFγ induced genes by directly binding to a specific DNA sequence and displacing the CEBP-β transcription factor. (D) Activated ERK1 and ERK2 regulate the cell cycle entry by dislodging Rb from its interaction with lamin A. Rb is released to the nucleoplasm and is rapidly phosphorylated and inactivated, leading to activation of the transcription factor E2F and cell cycle entry. (E) p38 inhibits cell cycle progression by blocking Mirk/Dyrk1B transcriptional activity in proliferating cells.