Raf-interactome in tuning the complexity and diversity of Raf function.

Raf kinases have been intensely studied subsequent to their discovery 30 years ago. The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase/mitogen-activated protein kinase (Ras-Raf-MEK-ERK/MAPK) signaling pathway is at the heart of the signaling networks that control many fundamental cellular processes and Raf kinases takes centre stage in the MAPK pathway, which is now appreciated to be one of the most common sources of the oncogenic mutations in cancer. The dependency of tumors on this pathway has been clearly demonstrated by targeting its key nodes; however, blockade of the central components of the MAPK pathway may have some unexpected side effects. Over recent years, the Raf-interactome or Raf-interacting proteins have emerged as promising targets for protein-directed cancer therapy. This review focuses on the diversity of Raf-interacting proteins and discusses the mechanisms by which these proteins regulate Raf function, as well as the implications of targeting Raf-interacting proteins in the treatment of human cancer.