Zizimin1, a novel Cdc42 activator, reveals a new GEF domain for Rho proteins

Nat Cell Biol. 2002 Sep;4(9):639-47. doi: 10.1038/ncb835.


The Rho family GTPases Rac, Rho and Cdc42 are critical in regulating the actin-based cytoskeleton, cell migration, growth, survival and gene expression. These GTPases are activated by guanine nucleotide-exchange factors (GEFs). A biochemical search for Cdc42 activators led to the cloning of zizimin1, a new protein whose overexpression induces Cdc42 activation. Sequence comparison combined with mutational analysis identified a new domain, which we named CZH2, that mediates direct interaction with Cdc42. CZH2-containing proteins constitute a new superfamily that includes the so-called 'CDM' proteins that bind to and activate Rac. Together, the results suggest that CZH2 is a new GEF domain for the Rho family of proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cloning, Molecular
  • Enzyme Activation
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • cdc42 GTP-Binding Protein / metabolism*
  • rho GTP-Binding Proteins / metabolism*


  • DOCK9 protein, human
  • Guanine Nucleotide Exchange Factors
  • RNA, Messenger
  • cdc42 GTP-Binding Protein
  • rho GTP-Binding Proteins