Chromatin-tethered MAPKs

Abstract

Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that are essential nodes in many cellular regulatory circuits including those that take place on DNA. Most members of the four MAPK subgroups that exist in canonical three kinase cascades-extracellular signal-regulated kinases 1 and 2 (ERK1/2), ERK5, c-Jun N-terminal kinases (JNK1-3), and p38 (α, β, γ, and δ) families-have been shown to perform regulatory functions on chromatin. This review offers a brief update on the variety of processes that involve MAPKs and available mechanisms garnered in the last two years.

Figure 1. Structural comparison of a bacterial transcription factor bound to DNA and the mammalian MAPK, ERK2

Front (top panels) and side (bottom panels) views of the bacterial transcription factor pair HipA/HipB complexed to DNA display structural similarity at a binding interface to the ERK2 MAPK insert (dark blue) which has been implicated in DNA binding. PDB: 3DNV and 1ERK.

Figure 2. MAPKs interact with chromatin through direct interactions with DNA as well as binding to chromatin-associated substrates

Examples of each interaction from the MAPK family are provided. Among chromatin-associated substrates, MAPKs bind to transcription factors, RNA polymerase subunits, histone modifying complexes and ATP-dependent chromatin modifiers.