Does isoform diversity explain functional differences in the 14-3-3 protein family?
The 14-3-3 family of proteins was originally identified in 1967 as simply an abundant brain protein. However it took almost 25 years before the ubiquitous role of 14-3-3 in cell biology was recognized when it was found to interact with several signalling and proto-oncogene proteins. Subsequently 14-3-3 proteins were the first protein recognized to bind a discrete phosphoserine/threonine-binding motifs. In mammals the 14-3-3 protein family is comprised of seven homologous isoforms. The 14-3-3 family members are expressed in all eukaryotes and although no single conserved function of the 14-3-3s is apparent, their ability to bind other proteins seems a crucial characteristic. To date more than 300 binding partners have been identified, of which most are phosphoproteins. Consequently, it has become clear that 14-3-3 proteins are involved in the regulation of most cellular processes, including several metabolic pathways, redox-regulation, transcription, RNA processing, protein synthesis, protein folding and degradation, cell cycle, cytoskeletal organization and cellular trafficking. In this review we include recent reports on the regulation of 14-3-3 by phosphorylation, and discuss the possible functional significance of the existence of distinct 14-3-3 isoforms in light of recent proteomics studies. In addition we discuss 14-3-3 interaction as a possible drug target.
Kjarland
E
E
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway. endre.kjarland@biomed.uib.no
Keen
T J
TJ
Kleppe
R
R
D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D016415:Sequence Alignment
D048948:14-3-3 Proteins; D008024:Ligands; C000715470:MAS1 protein, human; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D029701:Saccharomyces cerevisiae Proteins