Control of the hippo pathway by Set7-dependent methylation of Yap

Dev Cell. 2013 Jul 29;26(2):188-94. doi: 10.1016/j.devcel.2013.05.025. Epub 2013 Jul 11.

Abstract

Methylation of nonhistone proteins is emerging as a regulatory mechanism to control protein function. Set7 (Setd7) is a SET-domain-containing lysine methyltransferase that methylates and alters function of a variety of proteins in vitro, but the in vivo relevance has not been established. We found that Set7 is a modifier of the Hippo pathway. Mice that lack Set7 have a larger progenitor compartment in the intestine, coinciding with increased expression of Yes-associated protein (Yap) target genes. Mechanistically, monomethylation of lysine 494 of Yap is critical for cytoplasmic retention. These results identify a methylation-dependent checkpoint in the Hippo pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Cycle Proteins
  • Cells, Cultured
  • Methylation
  • Mice
  • Mice, Knockout
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Methyltransferases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Phosphoproteins
  • Yap protein, mouse
  • Protein Methyltransferases
  • Setd7 protein, mouse
  • Hippo protein, mouse
  • Protein-Serine-Threonine Kinases