Post-translational modifications have important roles in regulating protein function. Histone proteins, for example, are covalently modified on amino-acid residues in their tail regions, and different combinations of post-translational modifications on histone tails are thought to mediate unique cellular responses — a concept that is known as the 'histone code'. The current paradigm is that specific histone modifications serve as molecular marks for the recruitment of effector proteins that mediate downstream effects.

Cyrus Martin and Yi Zhang (page 838) — in an attempt to elucidate the role of histone modifications in cell function — focus on the methylation of histone proteins on lysine residues and the enzymes that mediate these site-specific methylation events. The characterization of these enzymes has revealed important functions of histone lysine methylation, ranging from heterochromatin formation and X-chromosome inactivation to transcriptional regulation. Now, what remains is to define the molecular events that link these histone modifications to the various specific biological outcomes.

An entirely different mode of regulation is illustrated in the Review by Walter Kolch on page 827. The Ras–MAPK signal transduction pathway is involved in many cellular processes such as cell proliferation, survival, differentiation and motility. Recently, a number of so-called scaffolding proteins have been identified, which can modulate the Ras pathway at different levels — not only can they regulate the signal flux and integrate and distribute signals, scaffolds also mediate crosstalk with other pathways. So, whereas high-throughput genetic and proteomic screening methods have dramatically enhanced our ability to systematically map protein interactions and reconstruct linear signalling networks, we are now facing the challenge to integrate these findings into a higher-level framework.