Signaling routes to CREM and CREB: plasticity in transcriptional activation

Trends Biochem Sci. 1999 Jul;24(7):281-5. doi: 10.1016/s0968-0004(99)01414-0.


The CREB and CREM transcription factors are activated by phosphorylation of a key serine residue by kinases stimulated by cyclic AMP, Ca2+, growth factors and stress signals. Phosphorylation allows recruitment of CREB-binding protein (CBP), a large co-activator that contacts the general transcriptional machinery. Studies of the physiological roles played by CREB and CREM have uncovered novel routes of transcriptional activation. For example, in male germ cells CREM is not phosphorylated but associates with ACT, a member of the LIM-only class of proteins that has intrinsic transcriptional activity. Thus, in some circumstances, CREM can bypass the classical requirement for phosphorylation and association with CBP.

Publication types

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

MeSH terms

  • Animals
  • CREB-Binding Protein
  • Cyclic AMP Response Element Modulator
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Male
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Repressor Proteins*
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcriptional Activation


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Trans-Activators
  • Cyclic AMP Response Element Modulator
  • CREB-Binding Protein