cCMP and cUMP: emerging second messengers

Trends Biochem Sci. 2015 Jan;40(1):8-15. doi: 10.1016/j.tibs.2014.10.008. Epub 2014 Nov 28.


The cyclic purine nucleotides cAMP and cGMP are established second messengers. By contrast, the existence of the cyclic pyrimidine nucleotides cytidine 3',5'-cyclic monophosphate (cCMP) and uridine 3',5'-cyclic monophosphate (cUMP) has been controversial for decades. The recent development of highly sensitive mass spectrometry (MS) methods allowed precise quantitation and unequivocal identification of cCMP and cUMP in cells. Importantly, cCMP and cUMP generators, effectors, cleaving enzymes, and transporters have now been identified. Here, I discuss evidence in support of cCMP and cUMP as bona fide second messengers, the emerging therapeutic implications of cCMP and cUMP signaling, and important unresolved questions for this field.

Keywords: bacterial toxins; cCMP; cUMP; nucleotidyl cyclases; phosphodiesterases; protein kinases.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Toxins / metabolism
  • Cyclic CMP / genetics
  • Cyclic CMP / metabolism*
  • Glucosyltransferases / genetics
  • Glucosyltransferases / metabolism*
  • Guanylate Cyclase / metabolism
  • Nucleotides, Cyclic / genetics
  • Nucleotides, Cyclic / metabolism*
  • Phosphoric Diester Hydrolases / metabolism
  • Protein Kinases / metabolism
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism
  • Uridine Monophosphate / genetics
  • Uridine Monophosphate / metabolism*


  • Bacterial Proteins
  • Bacterial Toxins
  • Nucleotides, Cyclic
  • Cyclic CMP
  • cyclic 3',5'-uridine monophosphate
  • Uridine Monophosphate
  • ExoY protein, bacteria
  • Glucosyltransferases
  • Protein Kinases
  • Phosphoric Diester Hydrolases
  • Adenylyl Cyclases
  • Guanylate Cyclase