Deciphering the retinoblastoma protein phosphorylation code

Trends Biochem Sci. 2013 Jan;38(1):12-9. doi: 10.1016/j.tibs.2012.10.007. Epub 2012 Dec 3.


Multisite phosphorylation modulates the function of regulatory proteins with complex signaling properties and outputs. The retinoblastoma tumor suppressor protein (Rb) is inactivated by cyclin-dependent kinase (Cdk) phosphorylation in normal and cancer cell cycles, so understanding the molecular mechanisms and effects of Rb phosphorylation is imperative. Rb functions in diverse processes regulating proliferation, and it has been speculated that multisite phosphorylation might act as a code in which discrete phosphorylations control specific activities. The idea of an Rb phosphorylation code is evaluated here in light of recent studies of Rb structure and function. Rb inactivation is discussed with an emphasis on how multisite phosphorylation changes Rb structure and associations with protein partners.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle / physiology*
  • Cyclin-Dependent Kinases / metabolism*
  • Humans
  • Phosphorylation
  • Protein Conformation
  • Retinoblastoma Protein / chemistry
  • Retinoblastoma Protein / metabolism*
  • Signal Transduction


  • Retinoblastoma Protein
  • Cyclin-Dependent Kinases